bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of Iporin as a novel interaction partner for rab1
Authors: Bayer Michael , Fischer Julia , Kremerskothen Joachim , Ossendorf Edith , Matanis Theodoros , Konczal Magdalena , Weide Thomas , Barnekow Angelika 
Published: March 2005

Abstract
Background
The small GTPase rab1a and its isoform rab1b are essential regulating components in the vesicle transport between the ER and the Golgi apparatus. Rab1 is thought to act as a molecular switch and can change between an active GTP-bound and an inactive GDP-bound conformation. To elucidate the function of rab1, several approaches have been established to isolate effector proteins, which interact with the activated conformation of rab1. To date p115, GM130, golgin-84 and MICAL have been identified as direct interacting partners. Together with rab1, these molecules are components of a protein complex, which mediates and regulates intracellular vesicle transport.

Results
Here, we report the characterization of Iporin, which is similar to KIAA0375 as a novel rab1-interacting protein. It was initially identified by yeast two-hybrid screening experiments with the active mutant of rab1b (rab1b Q67R) as bait. Iporin contains a SH3 domain and two polyproline stretches, which are known to play a role in protein/protein interactions. In addition, Iporin encloses a RUN domain, which seems to be a major part of the r ab1b inding domain (R1BD). Iporin is ubiquitously expressed and immunofluorescence staining displays a cytosolic punctual distribution. Interestingly, we also show that Iporin interacts with another rab1 interacting partner, the GM130 protein.

Conclusion
Our results demonstrate that Iporin is a potential new interacting partner of rab1. Iporin is different from already identified rab1 interacting proteins concerning protein structure and cellular localization. We conclude that Iporin might function as a link between the targeting of ER derived vesicles, triggered by the rab1 GTPase and a signaling pathway regulated by molecules containing SH3 and/or poly-proline regions. The characterization of this novel intermolecular relation could help to elucidate how vesicles find their way from ER to the Golgi apparatus.
Imaging plant cell death: GFP-Nit1 aggregation marks an early step of wound and herbicide induced cell death
Authors: Cutler Sean R , Somerville Chris R 
Published: March 2005

Abstract
Background
A great deal is known about the morphological endpoints of plant cell death, but relatively little is known about its sequence of events and / or its execution at the biochemical level. Live cell imaging using GFP-tagged markers is a powerful way to provide dynamic portraits of a cellular process that can in turn provide a descriptive foundation valuable for future biochemical and genetic investigations.

Results
While characterizing a collection of random GFP-protein fusion markers we discovered that mechanical wounding induces rapid aggregation of a GFP-Nitrilase 1 fusion protein in Arabidopsis cells directly abutting wound sites. Time-lapse imaging of this response shows that the aggregation occurs in cells that subsequently die 30 – 60 minutes post-wounding, indicating that GFP-Nit1 aggregation is an early marker of cell death at wound sites. Time-lapse confocal imaging was used to characterize wound-induced cell death using GFP-Nit1 and markers of the nucleus and endoplasmic reticulum. These analyses provide dynamic portraits of well-known death-associated responses such as nuclear contraction and cellular collapse and reveal novel features such as nuclear envelope separation, ER vesiculation and loss of nuclear-lumen contents. As a parallel system for imaging cell death, we developed a chemical method for rapidly triggering cell death using the herbicides bromoxynil or chloroxynil which cause rapid GFP-Nit1 aggregation, loss of nuclear contents and cellular collapse, but not nuclear contraction, separating this response from others during plant cell death.

Conclusion
Our observations place aggregation of Nitrilase 1 as one of the earliest events associated with wound and herbicide-induced cell death and highlight several novel cellular events that occur as plant cells die. Our data create a detailed descriptive framework for future investigations of plant cell death and provide new tools for both its cellular and biochemical analysis.
Practical considerations for estimating clinical trial accrual periods: application to a multi-center effectiveness study
Authors: Carter Rickey E , Sonne Susan C , Brady Kathleen T 
Published: March 2005

Abstract
Background
Adequate participant recruitment is vital to the conduct of a clinical trial. Projected recruitment rates are often over-estimated, and the time to recruit the target population (accrual period) is often under-estimated.

Methods
This report illustrates three approaches to estimating the accrual period and applies the methods to a multi-center, randomized, placebo controlled trial undergoing development.

Results
Incorporating known sources of accrual variation can yield a more justified estimate of the accrual period. Simulation studies can be incorporated into a clinical trial's planning phase to provide estimates for key accrual summaries including the mean and standard deviation of the accrual period.

Conclusion
The accrual period of a clinical trial should be carefully considered, and the allocation of sufficient time for participant recruitment is a fundamental aspect of planning a clinical trial.
Internal fixation of femoral shaft fractures in children by intramedullary Kirschner wires (a prospective study): its significance for developing countries
Authors: Chitgopkar Shashank D 
Published: March 2005

Abstract
Background
To evaluate internal fixation by intramedullary Kirschner wires as a surgical technique in the treatment of femoral shaft fractures in children by a prospective study.

Methods
17 femoral shaft fractures at various levels in 16 children aged 2–15 years were treated by closed intramedullary Kirschner wiring under image intensifier control between May 2000 and October 2003. No external splint was used.

Results
Fracture union was achieved in 6–14 weeks. Non-weight bearing crutch walking was started 2–3 days after surgery. Full weight bearing started 6–14 weeks. Average operative time was 40 min (range 20–72 min). Wires were removed after 8–22 weeks. There were no infections, no limb length disparity. One child had pin track ulceration. A big child of 14 years had angulation of the fracture.

Conclusion
Intramedullary nailing of femoral shaft fractures in children by stainless steel Kirschner wires is an effective method, which compares well with other studies. It is a simple procedure, which can be easily reproduced. Blood loss is minimal, and the operative time short. There is no need pre-bend the wires in a C or S curve. Stainless steel Kirschner wires are cheap, universally available, and can be manufactured locally. The cost of Image intensifiers is affordable in most of the cities of the developing countries. The hospital does not have to maintain a costly inventory. Provides early mobility, return to home and, school. Gives a predictable clinical pathway and reduces occupancy of hospital beds.
The technique was successfully applied for internal fixation of other diaphyseal fractures in children and some selected diaphyseal fractures in adults. Based on my experience and a review of the literature, I recommend this technique as a modality for treatment of femoral shaft fractures in children aged 2 to 14 years.
An ethical framework for cardiac report cards: a qualitative study
Authors: Richard Shawn A , Rawal Shail , Martin Douglas K 
Published: March 2005

Abstract
Background
The recent proliferation of health care report cards, especially in cardiac care, has occurred in the absence of an ethical framework to guide in their development and implementation. An ethical framework is a consistent and comprehensive theoretical foundation in ethics, and is formed by integrating ethical theories, relevant literature, and other critical information (such as the views of stakeholders). An ethical framework in the context of cardiac care provides guidance for developing cardiac report cards (CRCs) that are relevant and legitimate to all stakeholders. The purpose of this study is to develop an ethical framework for CRCs.

Methods
Delphi technique – 13 panelists: 2 administrators, 2 cardiac nurses, 5 cardiac patients, 2 cardiologists, 1 member of the media, and 1 outcomes researcher. Panelists' views regarding the ethics of CRCs were analyzed and organized into themes.

Results
We have organized panelists' views into ten principles that emerged from the data: 1) improving quality of care, 2) informed understanding, 3) public accountability, 4) transparency, 5) equity, 6) access to information 7) quality of information, 8) multi-stakeholder collaboration, 9) legitimacy, and 10) evaluation and continuous quality improvement.

Conclusion
We have developed a framework to guide the development and dissemination of CRCs. This ethical framework can provide necessary guidance for those generating CRCs and may help them avoid a number of difficult issues associated with existing ones.
Amplifier spurious input current components in electrode-electrolyte interface impedance measurements
Authors: Felice Carmelo J , Madrid Rossana E , Valentinuzzi Max E 
Published: March 2005

Abstract

Background
In Impedance Microbiology, the time during which the measuring equipment is connected to the bipolar cells is rather long, usually between 6 to 24 hrs for microorganisms with duplication times in the order of less than one hour and concentrations ranging from 101 to 107 [CFU/ml]. Under these conditions, the electrode-electrolyte interface impedance may show a slow drift of about 2%/hr. By and large, growth curves superimposed on such drift do not stabilize, are less reproducible, and keep on distorting all over the measurement of the temporal reactive or resistive records due to interface changes, in turn originated in bacterial activity. This problem has been found when growth curves were obtained by means of impedance analyzers or with impedance bridges using different types of operational amplifiers.

Methods
Suspecting that the input circuitry was the culprit of the deleterious effect, we used for that matter (a) ultra-low bias current amplifiers, (b) isolating relays for the selection of cells, and (c) a shorter connection time, so that the relays were maintained opened after the readings, to bring down such spurious drift to a negligible value. Bacterial growth curves were obtained in order to test their quality.

Results
It was demonstrated that the drift decreases ten fold when the circuit remained connected to the cell for a short time between measurements, so that the distortion became truly negligible. Improvement due to better-input amplifiers was not as good as by reducing the connection time. Moreover, temperature effects were insignificant with a regulation of ± 0.2 [°C]. Frequency did not influence either.

Conclusion
The drift originated either at the dc input bias offset current (Ios) of the integrated circuits, or in discrete transistors connected directly to the electrodes immersed in the cells, depending on the particular circuit arrangement. Reduction of the connection time was the best countermeasure.
Ocean climate and seal condition
Authors: Le Boeuf Burney J , Crocker Daniel E 
Published: March 2005

Abstract

Background

The condition of many marine mammals varies with fluctuations in productivity and food supply in the ocean basin where they forage. Prey is impacted by physical environmental variables such as cyclic warming trends. The weaning weight of northern elephant seal pups, Mirounga angustirostris, being closely linked to maternal condition, indirectly reflects prey availability and foraging success of pregnant females in deep waters of the northeastern Pacific. The aim of this study was to examine the effect of ocean climate on foraging success in this deep-diving marine mammal over the course of three decades, using cohort weaning weight as the principal metric of successful resource accrual.

Results

The mean annual weaning weight of pups declined from 1975 to the late 1990s, a period characterized by a large-scale, basin-wide warm decadal regime that included multiple strong or long-duration El Niños; and increased with a return to a cool decadal regime from about 1999 to 2004. Increased foraging effort and decreased mass gain of adult females, indicative of reduced foraging success and nutritional stress, were associated with high ocean temperatures.

Conclusion

Despite ranging widely and foraging deeply in cold waters beyond coastal thermoclines in the northeastern Pacific, elephant seals are impacted significantly by ocean thermal dynamics. Ocean warming redistributes prey decreasing foraging success of females, which in turn leads to lower weaning mass of pups. Annual fluctuations in weaning mass, in turn, reflect the foraging success of females during the year prior to giving birth and signals changes in ocean temperature cycles.
Long-term outcome of patients with diffuse proliferative lupus nephritis treated with prednisolone and oral cyclophosphamide followed by azathioprine
Authors: Chan T M , Tse K C , Tang C SO , Lai K N , Li F K 
Published: March 2005

The short-term outcome of patients with diffuse proliferative lupus nephritis (DPLN) has improved with advances in immunosuppressive treatment. However, the impact of different immunosuppressive regimens on long-term renal function remains to be defined. This prospective cohort study examined the long-term renal function and disease relapse in adults with biopsy-proven DPLN, significant proteinuria, and hypoalbuminemia, who had been treated with sequential immunosuppression comprising prednisolone and oral cyclophosphamide as induction followed by low-dose prednisolone and azathioprine as maintenance. Sixty-six patients with 68 episodes of DPLN were included, with follow-up of 91.7 + 36.7 months. 82.4% achieved complete remission and 39.1% relapsed during follow-up. Patients in partial remission were at higher risk of relapse compared with those in complete remission (hazard ratio 6.2, P, 0.001). Serum creatinine remained stable over time (P = 0.931), while creatinine clearance showed a significant increase with time after treatment (P = 0.032). Three (4.4%) patients had doubling of baseline creatinine, but none reached end-stage renal failure or died. Univariate and mixed model analyses showed that the evolution of long-term renal function was significantly influenced by the chronicity score and creatinine clearance at baseline, and by the renal function at one year after treatment. These data demonstrate the efficacy of sequential immunosuppression in preserving renal function in most Chinese subjects with DPLN. The results also indicate that irreversible renal scarring (as reflected by baseline chronicity score), renal reserve (as reflected by renal function at baseline and one year), and an induction regimen that is effective in preserving the nephron mass are critical determinants of long-term renal outcome.
Phase II Study of Efficacy, Safety, and Pharmacokinetics of Trastuzumab Monotherapy Administered on a 3-Weekly Schedule
Authors: Baselga José , Carbonell Xavier , Castañeda-Soto Noel-Jaime , Clemens Michael , Green Michael , Harvey Vernon , Morales Serafin , Barton Claire , Ghahramani Parviz 
Published: March 2005

Purpose This phase II study investigated the efficacy, safety, and pharmacokinetics of trastuzumab monotherapy given as first-line treatment once every 3 weeks (3-weekly) in women with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). Patients and Methods Patients with previously untreated HER2-positive MBC received a loading dose of trastuzumab, 8 mg/kg intravenously (IV) and then 6 mg/kg IV at 3-week intervals until disease progression or patient withdrawal. Results In total, 105 patients received a median of five cycles of therapy (range, 1 to 35+). The overall response rate was 19% (23% in patients with measurable centrally confirmed immunohistochemistry [IHC] 3+ and/or fluorescence in situ hybridization [FISH] -positive disease) and clinical benefit rate (complete and partial responses plus stable disease for at least 6 months) was 33% (36% in patients with measurable centrally confirmed IHC 3+ and/or FISH-positive disease). Median time to progression was 3.4 months (range, 0.6 to 23.6 months). The most common treatment-related adverse events were rigors, pyrexia, headache, nausea, and fatigue. Median baseline left ventricular ejection fraction was 63%; this did not significantly change over the course of the study. The average exposure to trastuzumab observed in this study was similar to that in previous studies of the weekly regimen. However, as expected, mean trough trastuzumab concentrations were lower and peak levels were higher with 3-weekly trastuzumab compared with weekly treatments. Conclusion Administering higher doses on a 3-weekly schedule did not compromise the efficacy and safety of trastuzumab in women with HER2-positive MBC, and average exposure was similar to that observed with weekly therapy. Three-weekly trastuzumab may represent a convenient alternative to weekly administration.
Extracapsular Extension of Pelvic Lymph Node Metastases From Urothelial Carcinoma of the Bladder Is an Independent Prognostic Factor
Authors: Fleischmann Achim , Thalmann George N. , Markwalder Regula , Studer Urs E. 
Published: March 2005

Purpose To analyze the prognostic impact of risk factors for urothelial carcinoma of the bladder (UCB) with pelvic lymph node (LN) metastases. Patients and Methods We analyzed a consecutive series of 507 patients with UCB who were preoperatively staged N0M0. One hundred one of 124 eligible patients who were treated with radical cystectomy and standardized extended bilateral pelvic lymphadenectomy with curative intent and had postoperatively confirmed LN metastases were evaluated in regard to recurrence-free and overall survival. Results A median of 22 nodes per patient (range, 10 to 43 nodes) were removed and examined. Median recurrence-free and overall survival durations were 17 months and 21 months (range for both, 1 to 191 months), respectively. In the multivariate analysis for recurrence-free survival, extracapsular extension of LN metastases was the strongest prognostic factor (P = .019). Other variables such as tumor stage (pT1/2 v pT3 and pT4), the number (< five v ≥ five), and the percentage (< 20% v ≥ 20%) of metastatic nodes had a significant influence on recurrence-free and overall survival in the univariate analysis. However, they all failed to be significant prognostic factors in the multivariate analysis. Conclusion The results of this study indicate that radical cystectomy with bilateral lymphadenectomy can have a curative effect in a subset of patients with pelvic LN positive UCB. Provided that a representative number of LNs are removed by meticulous lymphadenectomy and that a thorough histologic examination is performed, prognosis for such patients can be determined quite reliably. In the multivariate analysis, extracapsular extension of LN metastases was the strongest factor predicting prognosis.
Possible Future Issues in the Treatment of Glioblastomas: Special Emphasis on Cell Migration and the Resistance of Migrating Glioblastoma Cells to Apoptosis
Authors: Lefranc Florence , Brotchi Jacques , Kiss Robert 
Published: March 2005

Purpose The present review aims to emphasize that malignant gliomas are characterized by the diffuse invasion of distant brain tissue by a myriad of single migrating cells that exhibit decreased levels of apoptosis (programmed cell death type I), thus a resistance to cytotoxic insult. Methods The present review surveys the molecular mechanisms of migration in malignant gliomas and potential issues arising from treatments, in addition to relationships between glioma cell migration and resistance to apoptosis in terms of the molecular signaling pathways. Results Clinical and experimental data demonstrate that glioma cell migration is a complex combination of multiple molecular processes, including the alteration of tumor cell adhesion to a modified extracellular matrix, the secretion of proteases by the cells, and modifications to the actin cytoskeleton. Intracellular signaling pathways involved in the acquisition of resistance to apoptosis by migrating glioma cells concern PI3K, Akt, mTOR, NF-κB, and autophagy (programmed cell death type II). Conclusion A number of signaling pathways can be constitutively activated in migrating glioma cells, thus rendering these cells resistant to cytotoxic insults. However, these pathways are not all constitutively activated at the same time in any one glioma. Particular inhibitors should therefore only be chosen if the target is present in the tumor tissue, but this is only possible if individual patients are submitted to the molecular profiling of their tumors before undergoing any treatment to combat their migratory glioma cells. Specific antimigratory compounds should be added to conventional radio- and/or chemotherapy.
Efficacy of Prophylactic Mastectomy in Women With Unilateral Breast Cancer: A Cancer Research Network Project
Authors: Herrinton Lisa J. , Barlow William E. , Yu Onchee , Geiger Ann M. , Elmore Joann G. , Barton Mary B. , Harris Emily L. , Rolnick Sharon , Pardee Roy , Husson Gail , Macedo Ana , Fletcher Suzanne W. 
Published: March 2005

Purpose We investigated the efficacy of contralateral prophylactic mastectomy (CPM) in reducing contralateral breast cancer incidence and breast cancer mortality among women who have already been diagnosed with breast cancer. Methods This retrospective cohort study comprised approximately 50,000 women who were diagnosed with unilateral breast cancer during 1979 to 1999. Using computerized data confirmed by chart review, we identified 1,072 women (1.9%) who had CPM. We obtained covariate information for these women and for a sample of 317 women who did not undergo CPM. Results The median time from initial breast cancer diagnosis to the end of follow-up was 5.7 years. Contralateral breast cancer developed in 0.5% of women with CPM, metastatic disease developed in 10.5%, and subsequent breast cancer developed in 12.4%; 8.1% died from breast cancer. Contralateral breast cancer developed in 2.7% of women without CPM, and 11.7% died of breast cancer. After adjustment for initial breast cancer characteristics, treatment, and breast cancer risk factors, the hazard ratio (HR) for the occurrence of contralateral breast cancer after CPM was 0.03 (95% CI, 0.006 to 0.13). After adjustment for breast cancer characteristics and treatment, the HRs for the relationship of CPM with death from breast cancer, with death from other causes, and with all-cause mortality were 0.57 (95% CI, 0.45 to 0.72), 0.78 (95% CI, 0.57 to 1.06), and 0.60 (95% CI, 0.50 to 0.72), respectively. Conclusion CPM seems to protect against the development of contralateral breast cancer, and although women who underwent CPM had relatively low all-cause mortality, CPM also was associated with decreased breast cancer mortality.