bluuebunny/crossref_metadata_2025 huggingface dataset:
The μ Opioid Agonist Morphine Modulates Potentiation of Capsaicin-Evoked TRPV1 Responses through a Cyclic AMP-Dependent Protein Kinase a Pathway
Authors: Vetter Irina , Wyse Bruce D , Monteith Gregory R , Roberts-Thomson Sarah J , Cabot Peter J
Published: July 2006

Background

The vanilloid receptor 1 (TRPV1) is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA) pathway to potentiate TRPV1-mediated capsaicin responses. Such regulation may have significance in inflammatory pain. However, few functional receptor interactions that inhibit PKA-mediated potentiation of TRPV1 responses have been described.

Results

In the present studies we investigated the hypothesis that the μ opioid receptor (MOP) agonist morphine can modulate forskolin-potentiated capsaicin responses through a cAMP-dependent PKA pathway. HEK293 cells were stably transfected with TRPV1 and MOP, and calcium (Ca2+) responses to injection of the TRPV1 agonist capsaicin were monitored in Fluo-3-loaded cells. Pre-treatment with morphine did not inhibit unpotentiated capsaicin-induced Ca2+ responses but significantly altered capsaicin responses potentiated by forskolin. TRPV1-mediated Ca2+ responses potentiated by the direct PKA activator 8-Br-cAMP and the PKC activator Phorbol-12-myristate-13-acetatewere not modulated by morphine. Immunohistochemical studies confirmed that the TRPV1 and MOP are co-expressed on cultured Dorsal Root Ganglion neurones, pointing towards the existence of a functional relationship between the G-protein coupled MOP and nociceptive TRPV1.

Conclusion

The results presented here indicate that the opioid receptor agonist morphine acts via inhibition of adenylate cyclase to inhibit PKA-potentiated TRPV1 responses. Targeting of peripheral opioid receptors may therefore have therapeutic potential as an intervention to prevent potentiation of TRPV1 responses through the PKA pathway in inflammation.
Are bone erosions detected by magnetic resonance imaging and ultrasonography true erosions? A comparison with computed tomography in rheumatoid arthritis metacarpophalangeal joints
Authors: Døhn Uffe Møller , Ejbjerg Bo J , Court-Payen Michel , Hasselquist Maria , Narvestad Eva , Szkudlarek Marcin , Møller Jakob M , Thomsen Henrik S , Østergaard Mikkel
Published: July 2006

The objective of the study was, with multidetector computed tomography (CT) as the reference method, to determine whether bone erosions in rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints detected with magnetic resonance imaging (MRI) and ultrasonography (US), but not with radiography, represent true erosive changes. We included 17 RA patients with at least one, previously detected, radiographically invisible MCP joint MRI erosion, and four healthy control individuals. They all underwent CT, MRI, US and radiography of the 2nd to 5th MCP joints of one hand on the same day. Each imaging modality was evaluated for the presence of bone erosions in each MCP joint quadrant. In total, 336 quadrants were examined. The sensitivity, specificity and accuracy, respectively, for detecting bone erosions (with CT as the reference method) were 19%, 100% and 81% for radiography; 68%, 96% and 89% for MRI; and 42%, 91% and 80% for US. When the 16 quadrants with radiographic erosions were excluded from the analysis, similar values for MRI (65%, 96% and 90%) and US (30%, 92% and 80%) were obtained. CT and MRI detected at least one erosion in all patients but none in control individuals. US detected at least one erosion in 15 patients, however, erosion-like changes were seen on US in all control individuals. Nine patients had no erosions on radiography. In conclusion, with CT as the reference method, MRI and US exhibited high specificities (96% and 91%, respectively) in detecting bone erosions in RA MCP joints, even in the radiographically non-erosive joints (96% and 92%). The moderate sensitivities indicate that even more erosions than are seen on MRI and, particularly, US are present. Radiography exhibited high specificity (100%) but low sensitivity (19%). The present study strongly indicates that bone erosions, detected with MRI and US in RA patients, represent a loss of calcified tissue with cortical destruction, and therefore can be considered true bone erosions.
A cell-cycle independent role for p21 in regulating synovial fibroblast migration in rheumatoid arthritis
Authors: Woods James M , Klosowska Karolina , Spoden Darrin J , Stumbo Nataliya G , Paige Douglas J , Scatizzi John C , Volin Michael V , Rao Malathi S , Perlman Harris
Published: July 2006

Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and destruction of cartilage and bone. The fibroblast-like synoviocyte (FLS) population is central to the development of pannus by migrating into cartilage and bone. We demonstrated previously that expression of the cell cycle inhibitor p21 is significantly reduced in RA synovial lining, particularly in the FLS. The aim of this study was to determine whether reduced expression of p21 in FLS could alter the migratory behavior of these cells. FLS were isolated from mice deficient in p21 (p21(-/-)) and were examined with respect to growth and migration. p21(-/-) and wild-type (WT) FLS were compared with respect to migration towards chemoattractants found in RA synovial fluid in the presence and absence of cell cycle inhibitors. Restoration of p21 expression was accomplished using adenoviral infection. As anticipated from the loss of a cell cycle inhibitor, p21(-/-) FLS grow more rapidly than WT FLS. In examining migration towards biologically relevant RA synovial fluid, p21(-/-) FLS display a marked increase (3.1-fold; p < 0.05) in migration compared to WT cells. Moreover, this effect is independent of the cell cycle since chemical inhibitors that block the cell cycle have no effect on migration. In contrast, p21 is required to repress migration as restoration of p21 expression in p21(-/-) FLS reverses this effect. Taken together, these data suggest that p21 plays a novel role in normal FLS, namely to repress migration. Loss of p21 expression that occurs in RA FLS may contribute to excessive invasion and subsequent joint destruction.
Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases
Authors: Yamasaki Yoshioki , Narain Sonali , Hernandez Liza , Barker Tolga , Ikeda Keigo , Segal Mark S , Richards Hanno B , Chan Edward KL , Reeves Westley H , Satoh Minoru
Published: July 2006

Replication protein A (RPA), a heterotrimer with subunits of molecular masses 70, 32, and 14 kDa, is a single-stranded-DNA-binding factor involved in DNA replication, repair, and recombination. There have been only three reported cases of anti-RPA in systemic lupus erythematosus (SLE) and Sjögren syndrome (SjS). This study sought to clarify the clinical significance of autoantibodies against RPA. Sera from 1,119 patients enrolled during the period 2000 to 2005 were screened by immunoprecipitation (IP) of 35S-labeled K562 cell extract. Antigen-capture ELISA with anti-RPA32 mAb, immunofluorescent antinuclear antibodies (ANA) and western blot analysis with purified RPA were also performed. Our results show that nine sera immunoprecipitated the RPA70–RPA32–RPA14 complex and all were strongly positive by ELISA (titers 1:62,500 to 1:312,500). No additional sera were positive by ELISA and subsequently confirmed by IP or western blotting. All sera showed fine speckled/homogeneous nuclear staining. Anti-RPA was found in 1.4% (4/276) of SLE and 2.5% (1/40) of SjS sera, but not in rheumatoid arthritis (0/35), systemic sclerosis (0/47), or polymyositis/dermatomyositis (0/43). Eight of nine patients were female and there was no racial predilection. Other positive patients had interstitial lung disease, autoimmune thyroiditis/hepatitis C virus/pernicious anemia, or an unknown diagnosis. Autoantibody specificities found in up to 40% of SLE and other diseases, such as anti-nRNP, anti-Sm, anti-Ro, and anti-La, were unusual in anti-RPA-positive sera. Only one of nine had anti-Ro, and zero of nine had anti-nRNP, anti-Sm, anti-La, or anti-ribosomal P antibodies. In summary, high titers of anti-RPA antibodies were found in nine patients (1.4% of SLE and other diseases). Other autoantibodies found in SLE were rare in this subset, suggesting that patients with anti-RPA may form a unique clinical and immunological subset.
Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status
Authors: Souglakos John , Vamvakas Lambros , Apostolaki Stella , Perraki Maria , Saridaki Zacharenia , Kazakou Irine , Pallis Athanasios , Kouroussis Charalambos , Androulakis Nikos , Kalbakis Kostas , Millaki Georgia , Mavroudis Dimitris , Georgoulias Vassilis
Published: July 2006

Introduction

To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse.

Methods

The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR.

Results

The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007–0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51–101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97–12.84; P = 0.001) were independent predictive factors for CNS relapse.

Conclusion

CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs.
Epigenetic silencing and deletion of the BRCA1gene in sporadic breast cancer
Authors: Birgisdottir Valgerdur , Stefansson Olafur A , Bodvarsdottir Sigridur K , Hilmarsdottir Holmfridur , Jonasson Jon G , Eyfjord Jorunn E
Published: July 2006

Introduction

BRCA1 or BRCA2 germline mutations increase the risk of developing breast cancer. Tumour cells from germline mutation carriers have frequently lost the wild-type allele. This is predicted to result in genomic instability where cell survival depends upon dysfunctional checkpoint mechanisms. Tumorigenic potential could then be acquired through further genomic alterations. Surprisingly, somatic BRCA mutations are not found in sporadic breast tumours. BRCA1 methylation has been shown to occur in sporadic breast tumours and to be associated with reduced gene expression. We examined the frequency of BRCA1 methylation in 143 primary sporadic breast tumours along with BRCA1 copy number alterations and tumour phenotype.

Methods

Primary sporadic breast tumours were analysed for BRCA1α promoter methylation by methylation specific PCR and for allelic imbalance (AI) at BRCA1 and BRCA2 loci by microsatellite analysis and TP53 (also known as p53) mutations by constant denaturing gel electrophoresis. The BRCA1 methylated tumours were analysed for BRCA1 copy alterations by fluorescence in situ hybridisation and BRCA1 expression by immunostaining.

Results

BRCA1 methylation was found in 13/143 (9.1%) sporadic breast tumours. The BRCA1 methylated tumours were significantly associated with estrogen receptor (ER) negativity (P = 0.0475) and displayed a trend for BRCA1 AI (P = 0.0731) as well as young-age at diagnosis (≤ 55; P = 0.0898). BRCA1 methylation was not associated with BRCA2 AI (P = 0.5420), although a significant association was found between BRCA1 AI and BRCA2 AI (P < 0.0001).

Absent/markedly reduced BRCA1 expression was observed in 9/13 BRCA1 methylated tumours, most of which had BRCA1 deletion. An elevated TP53 mutation frequency was found among BRCA1 methylated tumours (38.5%) compared with non-methylated tumours (17.2%). The BRCA1 methylated tumours were mainly of tumour grade 3 (7/13) and infiltrating ductal type (12/13). Only one methylated tumour was of grade 1.

Conclusion

BRCA1 methylation is frequent in primary sporadic breast tumours. We found an indication for BRCA1 methylation to be associated with AI at the BRCA1 locus. Almost all BRCA1 methylated tumours with absent/markedly reduced BRCA1 expression (8/9) displayed BRCA1 deletion. Thus, epigenetic silencing and deletion of the BRCA1 gene might serve as Knudson's two 'hits' in sporadic breast tumorigenesis. We observed phenotypic similarities between BRCA1 methylated and familial BRCA1 tumours, based on BRCA1 deletion, TP53 mutations, ER status, young age at diagnosis and tumour grade.
How can the response to volume expansion in patients with spontaneous respiratory movements be predicted?
Authors: Heenen Sarah , De Backer Daniel , Vincent Jean-Louis
Published: July 2006

Introduction

The aim of the study was to evaluate the ability of different static and dynamic measurements of preload to predict fluid responsiveness in patients with spontaneous respiratory movements.

Methods

The subjects were 21 critically ill patients with spontaneous breathing movements receiving mechanical ventilation with pressure support mode (n = 9) or breathing through a face mask (n = 12), and who required a fluid challenge. Complete hemodynamic measurements, including pulmonary artery occluded pressure (PAOP), right atrial pressure (RAP), pulse pressure variation (ΔPP) and inspiratory variation in RAP were obtained before and after fluid challenge. Fluid challenge consisted of boluses of either crystalloid or colloid until cardiac output reached a plateau. Receiver operating characteristics (ROC) curve analysis was used to evaluate the predictive value of the indices to the response to fluids, as defined by an increase in cardiac index of 15% or more.

Results

Cardiac index increased from 3.0 (2.3 to 3.5) to 3.5 (3.0 to 3.9) l minute-1 m-2 (medians and 25th and 75th centiles), p < 0.05. At baseline, ΔPP varied between 0% and 49%. There were no significant differences in ΔPP, PAOP, RAP and inspiratory variation in RAP between fluid responders and non-responders. Fluid responsiveness was predicted better with static indices (ROC curve area ± SD: 0.73 ± 0.13 for PAOP, p < 0.05 vs ΔPP and 0.69 ± 0.12 for RAP, p = 0.054 compared with ΔPP) than with dynamic indices of preload (0.40 ± 0.13 for ΔPP and 0.53 ± 0.13 for inspiratory changes in RAP, p not significant compared with ΔPP).

Conclusion

In patients with spontaneous respiratory movements, ΔPP and inspiratory changes in RAP failed to predict the response to volume expansion.
Why Do Patients Choose Chemotherapy Near the End of Life? A Review of the Perspective of Those Facing Death From Cancer
Authors: Matsuyama Robin , Reddy Sashidhar , Smith Thomas J.
Published: July 2006

Purpose

The number of patients receiving chemotherapy near the end of life is increasing, as are concerns about goals of treatment, toxicity, and costs. We sought to determine the available sources of knowledge, the choices, and concerns of actual patients, and how patients balanced competing issues.

Methods

We used a literature search from 1980 to present.

Results

Available patient sources provide little information about prognosis, choices, alternatives, consequences, or how to choose. Many patients would choose chemotherapy for a small benefit in health outcomes, and for a smaller benefit than perceived by their health care providers for their own treatment. Adverse effects are less a concern for patients than for their well health care providers. There are no decision aids to assist patients with metastatic disease in making their choices, such as there are for adjuvant breast therapy.

Conclusion

The perspective of the patient is different from that of a well person. Patients are willing to undergo treatments that have small benefits with major toxicity. Receiving realistic information about the different options of care and the likelihood of successful treatment or adverse effects is difficult. These factors may explain some of the increased use of chemotherapy near the end of life. Decision aids and honest, unbiased sources to inform patients of their prognosis, choices, consequences, typical outcomes, and ways to make decisions are needed. More prospective information about how patients make their choices, and what they would consider a good choice, would assist informed decision making.
Phase I Trial of Oral Fenretinide in Children With High-Risk Solid Tumors: A Report From the Children's Oncology Group (CCG 09709)
Authors: Villablanca Judith G. , Krailo Mark D. , Ames Matthew M. , Reid Joel M. , Reaman Gregory H. , Reynolds C. Patrick
Published: July 2006

Purpose

To determine the maximal tolerated dosage (MTD) of oral fenretinide given as intact capsules for 7 days, repeated every 21 days, in children with high-risk solid tumors.

Methods

Children 21 years of age or younger received daily doses from 350 mg/m2to 3,300 mg/m2(divided into two or three doses), with pharmacokinetics during course one. The MTD was defined as zero to one of six patients with dose-limiting toxicity (DLT), with at least two of three or two of six DLT at next higher dose.

Results

Fifty-four patients, age 2 years to 20 years (median, 9 years), were treated: neuroblastoma (n = 39), Ewing sarcoma (n = 5), and other (n = 10). Prior therapy included autologous stem cell transplantation (n = 42), 13-cis-RA (n = 35), and 9-cis-RA (n = 1). One of four patients at 1,050 mg/m2with prior liver transplant had grade 3 ALT/abdominal pain/nausea/dehydration and grade 4 AST/emesis. At 1,860 mg/m2, one of seven patients had grade 3 hypoalbuminemia/hypophosphatemia. At 2,475 mg/m2, one of eight patients had grade 3 alkaline phosphatase; three of five patients had DLT at 3,300 mg/m2: grade 3 AST/ALT (n = 1), grade 4 bilirubin/grade 3 AST/ALT (n = 1), pseudotumor cerebri (n = 1). Pseudotumor cerebri also occurred at 600 mg/m2and 800 mg/m2. There was one complete response and 13 patients with stable disease (SD) for 8 or more courses in 30 assessable neuroblastoma patients. SD for 8 or more courses was seen in one of five Ewing sarcoma patients and one melanoma patient. Mean N-4-hydroxyphenyl retinamide plasma level (day 7, steady-state concentration) was 9.9 μmol/L at MTD.

Conclusion

The pediatric MTD of oral capsular fenretinide was 2,475 mg/m2per day, which achieved levels active against neuroblastoma in vitro with minimal toxicity. Response data support a phase II trial in neuroblastoma.
Trastuzumab in Combination With Heregulin-Activated Her-2 (erbB-2) Triggers a Receptor-Enhanced Chemosensitivity Effect in the Absence of Her-2 Overexpression
Authors: Menendez Javier A. , Mehmi Inderjit , Lupu Ruth
Published: July 2006

Purpose

The decision for treating breast cancer patients with trastuzumab is based on HER-2 amplification and/or overexpression.

Methods

Using MCF-7 cells (Her-2 ±) engineered to overexpress heregulin (MCF-7/HRG), a ligand for the Her-2/3/4 network, we investigated whether HRG-induced transactivation of Her-2 affected breast cancer cell sensitivity to chemotherapy and whether trastuzumab trigger receptor-enhanced chemosensitivity (REC) when combined with chemotherapy without Her-2 overexpression.

Results

MCF-7/HRG cells were more than 10-fold resistant to the alkylating agent cisplatin (CDDP), while trastuzumab coexposure completely reversed HRG-promoted CDDP resistance. A synergistic interaction between trastuzumab in combination with CDDP (paclitaxel or vincristine) was obtained in MCF-7/HRG cells. Trastuzumab prevented activation of the antiapoptotic and proliferative cascades and inhibited HRG-induced Her-2/3 phosphorylation. CDDP efficacy was enhanced by trastuzumab in cells expressing endogenously high levels of HRG. Conversely, trastuzumab coexposure was ineffective in enhancing chemotherapy efficacy in cells that did not secrete HRG, such as MCF-7 cells overexpressing a structural mutated HRG isoform. Therefore, trastuzumab-induced REC, in the absence of Her-2 overexpression, occurs through the kinase activity of Her-2/3. Interestingly, HRG expression in tumor biopsies from invasive breast carcinomas (n = 189) revealed that, whereas the minority (12%) of Her-2 positive tumors (n = 60; 32%) demonstrated Her-2 phosphorylation, the majority (67%) of HRG-overexpressing and Her-2 tumors (n = 57; 30%) were in active Her-2 status.

Conclusion

We demonstrate that assessment of HRG expression and Her-2 activation define a particular breast cancer patient population for which trastuzumab plus CDDP or taxol are extremely efficient without Her-2 overexpression.
5-Hydroxytryptamine-3 Receptor Antagonist With or Without Short-Course Dexamethasone in the Prophylaxis of Radiation Induced Emesis: A Placebo-Controlled Randomized Trial of the National Cancer Institute of Canada Clinical Trials Group (SC19)
Authors: Wong Rebecca K.S. , Paul Nancy , Ding Keyue , Whitehead Marlo , Brundage Michael , Fyles Anthony , Wilke Derek , Nabid Abdenour , Fortin Andre , Wilson Don , McKenzie Michael , Ackerman Ida , Souhami Luis , Chabot Pierre , Pater Joseph
Published: July 2006

Purpose

To evaluate the effectiveness of prophylactic dexamethasone for the control of radiation induced emesis (RIE) when added to ondansetron during days 1 to 5 of fractionated radiotherapy. The study had two hypotheses: ondansetron and dexamethasone could provide superior control of RIE over ondansetron alone during the prophylactic period and; the combination could provide sustained control of RIE during subsequent fractions of radiotherapy.

Patients and Methods

Between May 2001 to Jan 2004, 211 patients receiving radiotherapy (≥ 15 fractions) to the upper abdomen were randomly assigned to receive ondanstron 8 mg bid with either dexamethasone 4 mg daily or placebo during fractions 1 to 5. Rescue antiemetics were provided.

Results

During the prophylactic period there was a trend for improved complete control of nausea in the dexamethasone arm (50% v 38%; P = .06) while complete and partial control of emesis, average nausea score, and use of rescue medications were similar in the two groups. During the overall study period patients receiving dexamethasone had better complete control of emesis (23% v 12%; P = .02) and a lower average nausea score (0.28 v 0.39; P = .03); there was a trend towards less use of rescue medications with dexamethasone (70% v 80%; P = .09); other outcomes were similar on the two arms. Quality of life analysis showed a significant difference in appetite.

Conclusion

The addition of dexamethasone to ondansetron as prophylaxis provides a modest improvement in protection against RIE during moderately emetogenic fractionated radiotherapy. It is a potentially useful addition to 5-hydroxytryptamine-3 receptor antagonists in this setting.
Double-Blind, Placebo-Controlled, Randomized Study of Eicosapentaenoic Acid Diester in Patients With Cancer Cachexia
Authors: Fearon Kenneth C.H. , Barber Matthew D. , Moses Alastair G. , Ahmedzai Sam H. , Taylor Gillian S. , Tisdale Michael J. , Murray Gordon D.
Published: July 2006

Purpose

Eicosapentaenoic acid (EPA) has been proposed to have specific anticachectic effects. This trial compared EPA diethyl ester with placebo in cachectic cancer patients for effects on weight and lean body mass.

Patients and Methods

Five hundred eighteen weight-losing patients with advanced gastrointestinal or lung cancer were studied in a multicenter, double-blind, placebo controlled trial. Patients were randomly assigned to receive a novel preparation of pure EPA at a dose of 2 g or 4 g daily or placebo (2g EPA, n = 175; 4 g EPA, n = 172; placebo, n = 171). Patients were assessed at 4 weeks and 8 weeks.

Results

The groups were well balanced at baseline. Mean weight loss at baseline was 18% (n = 518). Over the 8-week treatment period, both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival, weight, or other nutritional variables. There was, however, a trend in favor of EPA with analysis of the primary end point, weight, at 8 weeks showing a borderline, nonsignificant treatment effect (P = .066). Relative to placebo, mean weight increased by 1.2 kg with 2 g EPA (95% CI, 0 kg to 2.3 kg) and by 0.3 kg with 4g EPA (−0.9 kg to 1.5 kg).

Conclusion

The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia. Future studies should concentrate on other agents or combination regimens.
Multicentric Breast Cancer: A New Indication for Sentinel Node Biopsy—A Multi-Institutional Validation Study
Authors: Knauer Michael , Konstantiniuk Peter , Haid Anton , Wenzl Etienne , Riegler-Keil Michaela , Pöstlberger Sabine , Reitsamer Roland , Schrenk Peter
Published: July 2006

Purpose

Multicentric breast cancer has been considered to be a contraindication for sentinel node (SN) biopsy (SNB). In this prospective multi-institutional trial, SNB-feasibility and accuracy was evaluated in 142 patients with multicentric cancer from the Austrian Sentinel Node Study Group (ASNSG) and compared with data from 3,216 patients with unicentric cancer.

Patients and Methods

Between 1996 and 2004, 3,730 patients underwent SNB at 15 ASNSG-affiliated hospitals. Patient data were entered in a multicenter database. One hundred forty-two patients presented with multicentric invasive breast cancer and underwent SNB.

Results

Intraoperatively, a mean number of 1.67 SNs were excised (identification-rate, 91.5%). The incidence of SN metastases was 60.8% (79 of 130). This was confirmed by axillary lymph node dissection (ALND) in 125 patients. Of patients with positive SNs, 60.8% (48 of 79) showed involvement of nonsentinel nodes (NSNs), as did three patients with negative SNs (false-negative rate, 4.0). Sensitivity, negative predictive value, and overall accuracy were 96.0%, 93.3%, and 97.3%, respectively. Ninety-one percent of the patients underwent mastectomy, and 9% were treated with breast conserving surgery. None of the patients have shown axillary recurrence so far (mean follow-up, 28.8 months). Compared with 3,216 patients with unicentric cancer, there was a significantly higher rate of SN metastases as well as in NSNs, whereas there was no difference in detection and false-negative rates.

Conclusion

Multicentric breast cancer is a new indication for SNB without routine ALND in controlled trials. Given adequate quality control and an interdisciplinary teamwork of surgical, nuclear medicine, and pathology units, SNB is both feasible and accurate in this disease entity.
Aggressiveness of Familial Prostate Cancer
Authors: Kupelian Patrick A. , Reddy Chandana A. , Reuther Alwyn M. , Mahadevan Arul , Ciezki Jay P. , Klein Eric A.
Published: July 2006

Purpose

To report on the aggressiveness of sporadic versus familial prostate cancer.

Patients and Methods

The study sample consisted of 4,112 stage T1-3 prostate cancer patients. The outcome of interest was biochemical relapse-free survival (bRFS). The analysis was performed for two distinct time periods, 1986 to 1992 (year ≤ 1992) and 1993 to 2002 (year ≥ 1993), to encompass both the early and late prostate-specific antigen (PSA) eras.

Results

A positive family history (FH positive) was reported in 16%. The 10-year bRFS rates for patients with negative family history (FH negative) versus FH positive were 59% and 63%, respectively (P = .90). However, in the year ≤ 1992 period, the 10-year bRFS rates for FH negative versus FH positive were 45% and 34%, respectively (P = .015). In the year ≥ 1993 period, the 10-year bRFS rates for FH negative versus FH positive were 61% and 67%, respectively (P = .54). Multivariate analysis failed to reveal family history as an independent predictor of relapse (P = .42). However, in the subset of patients in each era, family history was an independent predictor of relapse only for those treated in the year ≤ 1992 period (P = .038).

Conclusion

Family history was an independent predictor of biochemical failure only early in the PSA era, and men with an FH positive presented with more favorable disease later in the PSA era. This suggests that with stage migration and improved therapy, the impact of family history on prognosis has become minimal. However, underlying genetic factors affecting prostate cancer behavior in individuals with familial prostate cancer may still be important in determining individual prognosis.
High Survival and Organ Function Rates After Primary Chemoradiotherapy for Intermediate-Stage Squamous Cell Carcinoma of the Head and Neck Treated in a Multicenter Phase II Trial
Authors: Cohen Ezra E.W. , Haraf Daniel J. , List Marcy A. , Kocherginsky Masha , Mittal Bharat B. , Rosen Fred , Brockstein Bruce , Williams Rosalyn , Witt Mary Ellyn , Stenson Kerstin M. , Kies Merrill S. , Vokes Everett E.
Published: July 2006

Purpose

Patients with intermediate-stage squamous cell carcinoma of the head and neck traditionally have been treated with initial surgical resection followed by radiotherapy (RT) alone or chemoradiotherapy. A previous study in this patient population reported a 91% locoregional control rate and 65% overall survival (OS) rate at 5 years, with chemoradiotherapy used as primary treatment. This study was undertaken to assess whether shortening treatment duration with hyperfractionated RT would be feasible and improve locoregional control, organ preservation, and progression-free survival.

Methods

Eligible patients with stage II or III disease received fluorouracil, hydroxyurea, and RT given twice daily on a week-on/week-off schedule. Quality-of-life scores were measured using three validated indexes.

Results

All 53 patients enrolled are included in the analysis, with a median follow-up of 42 months (range, 5 to 98 months). Grade 3 or 4 in-field mucositis was observed in 77% and 9%, respectively. No patients required surgical salvage at the primary tumor site (pathological complete response rate, 100%). The 3-year progression-free and OS rates are 67% and 78%, respectively. The 3-year disease-specific mortality rate is 7%. At the time of analysis, 87% of surviving patients do not require enteral feeding support. Quality-of-life and performance assessment indicated that, although acute treatment toxicities were severe, most patients returned to pretreatment function by 12 months.

Conclusion

Concurrent chemoradiotherapy with hyperfractionated RT is feasible in this patient population and yields high local control and cure rates. Compared with our historical control using once-daily fractionation, hyperfractionation is accompanied by increased acute in-field toxicity.
α4-Tubulin is involved in rapid formation of long microtubules to push apart the daughter centrosomes during earlyxDrosophilaembryogenesis
Authors: Venkei Zsolt , Gáspár Imre , Tóth Gábor , Szabad János
Published: July 2006

Although α4-tubulin comprises only about one-fifth of the α-tubulin pool in every Drosophila egg, in the absence of α4-tubulin - in eggs of the kavar0/- hemizygous females - only a tassel of short microtubules forms with two barely separated daughter centrosomes. We report that α4-tubulin is enriched in the long microtubules that embrace the nuclear envelope and suggest that they push apart daughter centrosomes along the nuclear perimeter during the initial cleavage divisions. In vitro tubulin polymerization showed that α4-tubulin is required for rapid tubulin polymerization. Since tubulin polymerization is slow inside eggs of the kavar0/- females, only short microtubules can form within the 4 to 5 minutes allowed for the process. A tassel of short microtubules with two barely separated centrosomes forms in every egg of the Kavar18c/+ females, in which the cytoplasm contains both wild-type and Kavar18c-encoded α4-tubulin with an E82K amino acid substitution (E82K-α4-tubulin). E82K-α4-tubulin is incorporated into the microtubules and renders them unstable. When injected into wild-type early cleavage embryos E82K-α4-tubulin slows down the formation of long microtubules and the separation of the daughter centrosomes. Surprisingly, when injected into late cleavage embryos E82K-α4-tubulin is non-toxic. Similarly, in the neuroblasts, ectopically expressed E82K-α4-tubulin becomes incorporated into the microtubules that grow sufficiently long and function normally.
Control of the AtMAP65-1 interaction with microtubules through the cell cycle
Authors: Smertenko Andrei P. , Chang Hsin-Yu , Sonobe Seiji , Fenyk Stepan I. , Weingartner Magdalena , Bögre Laci , Hussey Patrick J.
Published: July 2006

Cell division depends on the fine control of both microtubule dynamics and microtubule organisation. The microtubule bundling protein MAP65 is a `midzone MAP' essential for the integrity of the anaphase spindle and cell division. Arabidopsis thaliana MAP65-1 (AtMAP65-1) binds and bundles microtubules by forming 25 nm cross-bridges. Moreover, as AtMAP65-1 bundles microtubules in interphase, anaphase and telophase but does not bind microtubules in prophase or metaphase, its activity through the cell cycle must be under tight control. Here we show that AtMAP65-1 is hyperphosphorylated during prometaphase and metaphase and that CDK and MAPK are involved in this phosphorylation. This phosphorylation inhibits AtMAP65-1 activity. Expression of non-phosphorylatable AtMAP65-1 has a negative effect on mitotic progression resulting in excessive accumulation of microtubules in the metaphase spindle midzone causing a delay in mitosis. We conclude that normal metaphase spindle organisation and the transition to anaphase is dependent on inactivation of AtMAP65-1.
Upgrading of paper-grade pulps to dissolving pulps by nitren extraction: Optimisation of extraction parameters and application to different pulps
Authors: Janzon Ron , Puls Jürgen , Saake Bodo
Published: July 2006

Xylans were selectively removed from paper-grade pulps by nitren extraction to produce dissolving pulps. Extraction parameters were optimised for a birch kraft pulp regarding time, temperature, liquor/pulp ratio, and total nitren charge. Furthermore, the applicability of the method was investigated for two other kraft pulps obtained from eucalyptus and mixed softwood, and for one beech sulfite pulp. Extracted pulps were characterised regarding their carbohydrate content and Cuen viscosity. The nitren charge was a decisive factor for xylan removal and pulp purity. The combination of a high nitren concentration and low liquor/pulp ratio was most effective for xylan removal. However, a high liquor/pulp ratio with a lower nitren concentration proved to be more selective and minimised cellulose degradation as well. Glucomannans were almost insoluble under the extraction conditions investigated. Therefore, softwood pulps were not suitable for the upgrading of chemical pulps to dissolving pulps by nitren extraction. On the other hand, hardwood pulps obtained by kraft and sulfite processes contained 96–97% cellulose after nitren extraction.
The formation of aromatic end group structures in O-alkyl substituted celluloses under alkaline pulping conditions
Authors: Vikkula Anne , Vuorinen Tapani
Published: July 2006

UV resonance Raman (UVRR) spectroscopy was used to study changes in the structure of reducing end groups of O-alkyl substituted celluloses under conditions simulating the initial phase of soda pulping. The derivatives studied were carboxymethyl cellulose (CMC) with a degree of substitution (DS) of 0.58 and methyl cellulose (MC) with DS of 1.64–1.95. Hot alkaline treatments were carried out in solutions of sodium hydroxide (0.1–1 M) at 95°C in the presence of creosol as a lignin model compound. Alkali-stable aromatic end groups were generated in both cellulose ethers. Moreover, the end groups of methyl cellulose were extensively condensed with creosol. The results demonstrate that aromatisation and condensation depend on the pH and reaction time.
Kraft pulp from budworm-infested Jack pine
Authors: Zhu J.Y. , Myers Gary C.
Published: July 2006

This study evaluated the quality of kraft pulp from budworm-infested jack pine. The logs were classified as merchantable live, suspect, or merchantable dead. Raw materials were evaluated through visual inspection, analysis of the chemical composition, SilviScan measurement of the density, and measurement of the tracheid length. Unbleached pulps were then refined using a laboratory disk refiner. The mechanical and optical properties of handsheets made from the refined pulps were evaluated. Although budworm galleries may affect the physical integrity of the wood, they have no effect on pulp quality. Blue stain did not affect the handsheet brightness. The results indicate that merchantable dead jack pine trees are acceptable for kraft pulp production, with equivalent pulp yield.
Impact of drying temperature and pressing time factor on VOC emissions from OSB made of Scots pine
Authors: Makowski Mathias , Ohlmeyer Martin
Published: July 2006

Correlations between process parameters and VOC emissions from an oriented strand board (OSB) made of Scots pine (Pinus sylvestris L.) were demonstrated. Terpene and aldehyde emissions were affected by the pressing time factors in different ways: terpene emissions were lowered with elevated pressing times, whereas the formation of volatile aldehydes was accelerated. Drying temperature mainly affected the dynamics of aldehyde formation, with a clear rise and fall in aldehyde concentration after drying at elevated temperatures (170°C and >200°C). As a consequence of lower temperatures (120°C), aldehyde emissions from OSB constantly increased over the testing period. In spite of this context, a sustainable reduction in aldehyde emissions by adjusting the relevant process parameters does not seem to be feasible, as the concentrations released from all panels converged during emission testing.
Mechanical characterisation of wood-adhesive interphase cell walls by nanoindentation
Authors: Konnerth Johannes , Gindl Wolfgang
Published: July 2006

The elastic modulus, hardness, and creep factor of wood cell walls in the interphase region of four different adhesive bonds were determined by nanoindentation. In comparison with reference cell walls unaffected by adhesive, interphase cell walls from melamine-urea-formaldehyde (MUF) and phenol-resorcinol-formaldehyde (PRF) adhesive bonds showed improved hardness and reduced creep, as well as improved elastic modulus in the case of MUF. In contrast, cell walls from the interphase region in polyvinylacetate (PVAc) and one-component polyurethane (PUR) bonds showed more creep, but lower elastic modulus and hardness than the reference. Considering the different cell-wall penetration behaviour of the adhesive polymers studied here, it is concluded that damage and loss of elastic modulus to surface cells occurring during the machining of wood is recovered in MUF and PRF bond lines, whereas damage of cell walls persists in PVAc and PUR bond lines.
Influence of variation in modulus of elasticity on creep of wood during changing process of moisture
Authors: Takahashi Chika , Nakazawa Noriko , Ishibashi Kazuyuki , Iida Ikuho , Furuta Yuzo , Ishimaru Yutaka
Published: July 2006

This study considered the influence of variations in the modulus of elasticity (MOE) on the mechano-sorptive (MS) creep of wood. MOE in the radial direction (ER) was investigated as a function of changes in moisture content (MC).ERvalues were lower during both adsorption and desorption processes than under constant MC, despite the same MC values. However, the effects observed were small and are thus not of great practical importance.
Quantification of Coarse Aggregate Surface Texture Using Image Analysis
Authors: Pan T , Tutumluer E
Published: July 2006

Aggregate surface texture affects the performance of pavement and railroad track structural layers, such as the unbound aggregate base/ballast, asphalt concrete, and Portland cement concrete. A quantitative surface texture (ST) index is defined in this paper based on image analysis to measure the irregularities on the surface of coarse aggregate particles in the extent that is not characterized by the commonly used large-scale morphological descriptors, such as flatness, elongation, and angularity. Using an image analysis approach referred to as erosion and dilation, the new ST index quantifies the coarse aggregate surface irregularities at the pixel level. Samples of natural gravel and crushed aggregate were used in establishing a realistic range for the ST index independent of particle size. The effectiveness and practical applicability of the defined ST index in characterizing aggregate surface texture were evaluated by measuring surface irregularities or texture of commonly used coarse aggregate materials.
Verfolgung, Selbsthilfe, Liquidation. Jüdische Genossenschaftsbanken im nationalsozialistischen Deutschland 1933–1938
Authors: Fischer Albert
Published: July 2006

Vorspann

Anders als über die jüdischen Privatbanken im Dritten Reich wissen wir über die meist erst 1933 entstehenden Genossenschaftsbanken noch immer recht wenig. Ihre wechselvolle Geschichte, in der sich die Verdrängung der Juden aus der deutschen Wirtschaft spiegelt, untersucht Albert Fischer mit Blick auf mehrere Fragen: Welches waren die Gründe für das sprunghafte Wachstum der jüdischen Genossenschaftsbanken seit 1933? Wie entwickelte sich ihr Verhältnis zur „arischen“ Bankenwelt und zu den Behörden des NS-Staates? Und weshalb schließlich konnten sich Reichsinnen- und Reichswirtschaftsministerium 1937/38 bei der Zerschlagung dieser Banken gegen das Justiz- und Arbeitsministerium durchsetzen?
Zwischen Pax Americana und Pakt Atomica. Das deutsch-amerikanische Verhältnis während der EURATOM-Verhandlungen 1955–1957
Authors: Segers Mathieu L.L.
Published: July 2006

Vorspann

Die Gründung der Europäischen Atomgemeinschaft (EURATOM) war mehr als nur ein innereuropäischer Prozess. Anhand neuer Akten kann der Verfasser nachweisen, dass die Politik, die die Bundesregierung in dieser Frage verfolgte, nur im Kontext der amerikanischen Außenpolitik verstanden werden kann.
Optimal Foraging Theory and the Racecar Driver: The Impact of Student‐Centered Learning on Anthropological Pedagogy
Authors: Mazur‐Stommen Susan
Published: July 2006

This article contributes to the field of anthropological pedagogy, adding to recent articles regarding needed change in anthropology teaching methods. All have in common the practice of anthropology in the classroom. The author used the theory of optimal foraging to encourage students to operationalize human behavior. The economic benefit that students reaped warrants discussion. Students rapidly and measurably improved several areas of their lifestyle including health, finance, and home. Pursuing an anthropology degree thus becomes a personal journey.
Film in the Undergraduate Anthropology Classroom: Applying Audience Response Research in Pedagogical Practice
Authors: Bird S. Elizabeth , Godwin Jonathan P.
Published: July 2006

While we often assume media are highly effective tools for learning, research shows an unpredictable relationship between text and audience response, with variable interpretation being the norm. This can be especially problematic in anthropology, whose central goal is to understand different cultures; some studies suggest that films may reinforce ethnocentrism, especially if used without framing or analysis. We report on a project that studied student responses to media, offering practical guidelines for effective use in the classroom.
Social Identity and the Yup'ik Eskimo Village Tunnel System in Precolonial and Colonial Western Coastal Alaska
Authors: Frink Lisa
Published: July 2006

Some western Alaskan coastal prehistoric and protohistoric village sites had intrasite semisubterranean passageways that connected the village men's house(s) and the smaller family houses. These tunnels acted as an interstitial and negotiated space that connected the gendered spatial spheres of Yup'ik Eskimo women and men. Instead of examining a newly constructed space that may have transformed relationships, this work examines the historically contingent consequence of the loss of these tunnels as a built medium, both between women and men and among women. It is my contention that the dismantling of the multipurpose village tunnels insulated women from one another, from their established methods for learning and means for building influence and authority, and from intimate engagement with the expanding mercantilist economy and equitable access to social and economic resources.
Analogic Reasoning, Ethnoarchaeology, and the Impact of Canines on the Archaeological Record
Authors: Kuznar Lawrence A. , Jeske Robert
Published: July 2006

Archaeologists have become aware that the ways they have used ethnographic analogy provide only limited ability to make inferences about the past. This apparent tyranny of the ethnographic record has caused a crisis for many archaeologists, as well as ethnoarchaeologists. Susan Kent remained a strong defender of analogic reason and encouraged ethnoarchaeologists to use analogy to create a better inferential structure for interpreting archaeological residues. We explore the philosophical basis of analogy in scientific reasoning and demonstrate how recent studies of canine activity on site structure can be used for inferring the presence of canines at prehistoric sites and the roles they played in prehistoric societies.
Archaeology and Environment–Behavior Studies
Authors: Rapoport Amos
Published: July 2006

This chapter clarifies my position vis‐à‐vis both the “New Archaeology” and current approaches. It briefly describes environment–behavior studies (EBS) and discusses the mutual relevance of the two fields, emphasizing the role EBS can play in archaeological inference. Examples, mainly from the post‐1990s archaeological literature, are used to support the argument.
Small Mammal Bones on Later Stone Age Sites from the Cape (South Africa): Consumption and Ritual Events
Authors: Parkington John , Fisher John W.
Published: July 2006

The Dunefield Midden site, located on the Atlantic coast of South Africa, contains abundant, well‐preserved animal bones and other archaeological materials believed to reflect multiple short occupations by hunter‐gatherer peoples several centuries ago. The bones of small mammals, constituting a subset of a large assemblage of vertebrate remains, present intriguing patterns with respect to spatial distributions of bones and of cutmarked bones. Pronounced differences in the spatial distributions of bones between small carnivores and small noncarnivores probably indicate differences in how the site occupants used the carcasses of these animals.