bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selection of gonadotrophin surge attenuating factor phage antibodies by bioassay
Authors: Sorsa-Leslie Tarja , Mason Helen D , Harris William J , Fowler Paul A 
Published: September 2005

Abstract

Background
We aimed to combine the generation of "artificial" antibodies with a rat pituitary bioassay as a new strategy to overcome 20 years of difficulties in the purification of gonadotrophin surge-attenuating factor (GnSAF).

Methods
A synthetic single-chain antibody (Tomlinson J) phage display library was bio-panned with partially purified GnSAF produced by cultured human granulosa/luteal cells. The initial screening with a simple binding immunoassay resulted in 8 clones that were further screened using our in-vitro rat monolayer bioassay for GnSAF. Initially the antibodies were screened as pooled phage forms and subsequently as individual, soluble, single-chain antibody (scAbs) forms. Then, in order to improve the stability of the scAbs for immunopurification purposes, and to widen the range of labelled secondary antibodies available, these were engineered into full-length human immunoglobulins. The immunoglobulin with the highest affinity for GnSAF and a previously described rat anti-GnSAF polyclonal antiserum was then used to immunopurify bioactive GnSAF protein. The two purified preparations were electrophoresed on 1-D gels and on 7 cm 2-D gels (pH 4–7). The candidate GnSAF protein bands and spots were then excised for peptide mass mapping.

Results
Three of the scAbs recognised GnSAF bioactivity and subsequently one clone of the purified scAb-derived immunoglobulin demonstrated high affinity for GnSAF bioactivity, also binding the molecule in such as way as to block its bioactivity. When used for repeated immunopurification cycles and then Western blot, this antibody enabled the isolation of a GnSAF-bioactive protein band at around 66 kDa. Similar results were achieved using the rat anti-GnSAF polyclonal antiserum. The main candidate molecules identified from the immunopurified material by excision of 2-D gel protein spots was human serum albumin precursor and variants.

Conclusion
This study demonstrates that the combination of bioassay and phage display technologies is a powerful tool in the study of uncharacterised proteins that defy conventional approaches. In addition, we conclude that these data support suggestions that GnSAF may be structurally related to serum albumin or very tightly bound to serum albumin.
Tositumomab and Iodine-131 Tositumomab Produces Durable Complete Remissions in a Subset of Heavily Pretreated Patients With Low-Grade and Transformed Non-Hodgkin’s Lymphomas
Authors: Fisher Richard I. , Kaminski Mark S. , Wahl Richard L. , Knox Susan J. , Zelenetz Andrew D. , Vose Julie M. , Leonard John P. , Kroll Stewart , Goldsmith Stanley J. , Coleman Morton 
Published: September 2005

PurposeThis study is an integrated efficacy analysis of the five clinical trials of tositumomab and iodine-131 tositumomab in patients with relapsed or refractory low-grade, follicular, or transformed low-grade non-Hodgkin’s lymphoma (NHL) that resulted in the regulatory approval of the iodine-131 tositumomab by the US Food and Drug Administration.Patients and MethodsThis integrated analysis included 250 patients. Patients received a single course of iodine-131 tositumomab. Responses were assessed by an independent panel of radiologists and oncologists.ResultsResponse rates in the five trials ranged from 47% to 68%; complete response rates ranged from 20% to 38%. With a median follow-up of 5.3 years, the 5-year progression-free survival was 17%. Eighty-one (32%) of 250 patients had a time to progression of ≥ 1 year (termed durable response population). For the durable response population, 44% had not progressed at ≥ 2.5 to ≥ 9.5 years and had a median duration of response of 45.8 months. The median duration of complete response was not reached. The durable response population had many poor prognostic characteristics, including bone marrow involvement (41%), bulky disease ≥ 5 cm (49%), and transformed histology (23%). Forty-three percent of the patients had been treated with more than four prior therapies and 36% had not responded to their most recent therapy.ConclusionThe tositumomab and iodine-131 tositumomab therapeutic regimen produces high response rates in patients with relapsed or refractory low-grade, follicular, and transformed low-grade NHL, with a sizable subgroup of patients achieving long-term durable responses.
Prognostic Factors and Life Expectancy in Myelodysplastic Syndromes Classified According to WHO Criteria: A Basis for Clinical Decision Making
Authors: Malcovati Luca , Porta Matteo Giovanni Della , Pascutto Cristiana , Invernizzi Rosangela , Boni Marina , Travaglino Erica , Passamonti Francesco , Arcaini Luca , Maffioli Margherita , Bernasconi Paolo , Lazzarino Mario , Cazzola Mario 
Published: September 2005

Purpose The aim of this study was to evaluate the prognostic value of the WHO proposal, to assess the role of the main prognostic factors in myelodysplastic syndromes (MDSs) classified into WHO subgroups, and to estimate mortality (standardized mortality ratio [SMR]) and life expectancy in these groups as a basis for clinical decision making. Patients and Methods Four hundred sixty-seven patients who were diagnosed as having de novo MDS at the Division of Hematology, University of Pavia (Pavia, Italy), between 1992 and 2002, were evaluated retrospectively for clinical and hematologic features at diagnosis, overall survival (OS), and progression to leukemia (leukemia-free survival). Results Significant differences in survival were noted between patients with refractory anemia (RA), refractory cytopenia with multilineage dysplasia, RA with excess blasts, type 1 (RAEB-1), and RAEB-2. The effect of demographic factors on OS was observed in MDS patients without excess blasts (age, P = .001; sex, P = .006), as in the general population. The mortality of RA patients 70 years or older did not differ significantly from that of the general population (SMR, 1.62; P = .06). Cytogenetics was the only International Prognostic Scoring System variable showing a prognostic value in MDS classified into WHO subgroups. Transfusion-dependent patients had a significantly shorter survival than patients who did not require transfusions (P < .001). Developing a secondary iron overload significantly affected the survival of transfusion-dependent patients (P = .003). Conclusion These data show that the WHO classification of MDSs has a relevant prognostic value. This classification, along with cytogenetics, might be useful in decisions regarding transplantation. MDS with isolated erythroid lineage dysplasia identifies a subset of truly low-risk patients, for whom a conservative approach is advisable.
Early Allogeneic Stem-Cell Transplantation for Young Adults With Acute Myeloblastic Leukemia in First Complete Remission: An Intent-to-Treat Long-Term Analysis of the BGMT Experience
Authors: Jourdan Eric , Boiron Jean-Michel , Dastugue Nicole , Vey Norbert , Marit Gérald , Rigal-Huguet Françoise , Molina Lysiane , Fegueux Nathalie , Pigneux Arnaud , Recher Christian , Rossi Jean-François , Attal Michel , Sotto Jean-Jacques , Maraninchi Dominique , Reiffers Josy , Bardou Valerie-Jeanne , Esterni Benjamin , Blaise Didier 
Published: September 2005

Purpose We analyzed the impact of allogeneic stem-cell transplantation (alloSCT) as an early consolidation for young patients with acute myeloblastic leukemia in first complete remission (CR1) through four successive protocols. Patients and Methods Of the 472 patients who achieved CR1, 182 (38%) had an HLA-identical sibling (donor group), and alloSCT was performed in 171 patients (94%). Of the 290 patients without donor (no-donor group), 62% received an autologous SCT. Results In an intent-to-treat analysis based on donor availability, the overall 10-year survival probability was 51% v 43% (P = .11) for the donor and no-donor groups, respectively. A Cox analysis determined that four factors had independent prognostic significance for survival (initial WBC count, French-American-British subtypes, cytogenetic risk, and number of induction courses). This permitted constitution of a simple index that reclassified 21% of the patients compared with usual cytogenetic classification and identified three subpopulations with different outcome and different impact of alloSCT. Conclusion AlloSCT was associated with a survival advantage for an intermediate-risk group. In other groups, numbers are limited for definitive conclusion. However, early performed alloSCT does not seem to be the optimal treatment of high-risk patients or offer any advantage over intensive chemotherapy in low-risk patients.
A prospective, randomised, controlled trial of the use of drains in total hip arthroplasty
Authors: Walmsley P. J. , Kelly M. B. , Hill R. M. F. , Brenkel I. 
Published: September 2005

The routine use of surgical drains in total hip arthroplasty remains controversial. They have not been shown to decrease the rate of wound infection significantly and can provide a retrograde route for it. Their use does not reduce the size or incidence of post-operative wound haematomas. This prospective, randomised study was designed to evaluate the role of drains in routine total hip arthroplasty.We investigated 552 patients (577 hips) undergoing unilateral or bilateral total hip arthroplasty who had been randomised to either having a drain for 24 hours or not having a drain. All patients followed standardised pre-, intra-, and post-operative regimes and were independently assessed using the Harris hip score before operation and at six, 18 and 36 months follow-up.The rate of superficial and deep infection was 2.9% and 0.4%, respectively, in the drained group and 4.8% and 0.7%, respectively in the undrained group. One patient in the undrained group had a haematoma which did not require drainage or transfusion. The rate of transfusion after operation in the drained group was significantly higher than for undrained procedures (p < 0.042). The use of a drain did not influence the post-operative levels of haemoglobin, the revision rates, Harris hip scores, the length of hospital stay or the incidence of thromboembolism. We conclude that drains provide no clear advantage at total hip arthroplasty, represent an additional cost, and expose patients to a higher risk of transfusion.
Recombinant human vascular endothelial growth factor enhances bone healing in an experimental nonunion model
Authors: Eckardt H. , Ding M. , Lind M. , Hansen E. S. , Christensen K. S. , Hvid I. 
Published: September 2005

The re-establishment of vascularity is an early event in fracture healing; upregulation of angiogenesis may therefore promote the formation of bone. We have investigated the capacity of vascular endothelial growth factor (VEGF) to stimulate the formation of bone in an experimental atrophic nonunion model. Three groups of eight rabbits underwent a standard nonunion operation. This was followed by interfragmentary deposition of 100 μg VEGF, carrier alone or autograft. After seven weeks, torsional failure tests and callus size confirmed that VEGF-treated osteotomies had united whereas the carrier-treated osteotomies failed to unite. The biomechanical properties of the groups treated with VEGF and autograft were identical. There was no difference in bone blood flow. We considered that VEGF stimulated the formation of competent bone in an environment deprived of its normal vascularisation and osteoprogenitor cell supply. It could be used to enhance the healing of fractures predisposed to nonunion.
Fractures of distally-fixed femoral stems after revision arthroplasty
Authors: Busch C. A. , Charles M. N. , Haydon C. M. , Bourne R. B. , Rorabeck C. H. , MacDonald S. J. , McCalden R. W. 
Published: September 2005

We identified five (2.3%) fractures of the stem in a series of 219 revision procedures using a cementless, cylindrical, extensively porous-coated, distally-fixed femoral stem. Factors relating to the patients, the implant and the operations were compared with those with intact stems. Finite-element analysis was performed on two of the fractured implants. Factors associated with fracture of the stem were poor proximal bone support (type III–type IV; p = 0.001), a body mass index > 30; (p = 0.014), a smaller diameter of stem (< 13.5 mm; p = 0.007) and the use of an extended trochanteric osteotomy (ETO 4/5: p = 0.028). Finite-element analysis showed that the highest stresses on the stem occurred adjacent to the site of the fracture. The use of a strut graft wired over an extended trochanteric osteotomy in patients lacking proximal femoral cortical support decreased the stresses on the stem by 48%. We recommend the use of a strut allograft in conjunction with an extended trochanteric osteotomy in patients with poor proximal femoral bone stock.
Safety and efficacy of the extended iliofemoral approach in the treatment of complex fractures of the acetabulum
Authors: Griffin D. B. , Beaulé P. E. , Matta J. M. 
Published: September 2005

There remains uncertainty about the most effective surgical approach in the treatment of complex fractures of the acetabulum. We have reviewed the experience of a single surgeon using the extended iliofemoral approach, as described by Letournel. A review of the database of such fractures identified 106 patients operated on using this approach with a minimum follow-up of two years. All data were collected prospectively. The fractures involved both columns in 64 (60%). Operation was undertaken in less than 21 days after injury in 71 patients (67%) and in 35 (33%) the procedure was carried out later than this. The reduction of the fracture was measured on plain radiographs taken after operation and defined as anatomical (0 to 1 mm of displacement); imperfect (2 to 3 mm) or poor (> 3 mm). The functional outcome was measured by the modified Merle d’Aubigné and Postel score. The mean follow-up was for 6.3 years (2 to 17). All patients achieved union of the fractures. The reduction was graded as anatomical in 76 (72%) of the patients, imperfect in 23 (22%), and poor in six (6%). The mean Merle d’Aubigné and Postel score was 15 (5 to 18) with 68 patients (64%) showing good or excellent and 38 (36%) fair or poor results. Function correlated significantly with the accuracy of the reduction (p < 0.009). Significant heterotopic ossification developed in 32 patients (30%) and was associated with a worse mean Merle d’Aubigné and Postel score of 13.7. The extended iliofemoral approach can be performed safely in selected complex acetabular fractures with an acceptable clinical outcome and rate of complications. Effective prophylaxis against heterotopic ossification should be strongly considered.
Five-year clinical, radiological and postmortem results of the Cambridge Cup in patients with displaced fractures of the neck of the femur
Authors: Field R. E. , Rushton N. 
Published: September 2005

The Cambridge Cup has been designed to replace the horseshoe-shaped articular cartilage of the acetabulum and the underlying subchondral bone. It is intended to provide physiological loading with minimal resection of healthy bone. The cup has been used in 50 women with displaced, subcapital fractures of the neck of the femur. In 24 cases, the cup was coated with hydroxyapatite. In 26, the coating was removed before implantation in order to simulate the effect of long-term resorption. The mean Barthel index and the Charnley-modified Merle d’Aubigné scores recovered to their levels before fracture. We reviewed 30 women at two years, 21 were asymptomatic and nine reported minimal pain. The mean scores deteriorated slightly after five years reflecting the comorbidity of advancing age. Patients with the hydroxyapatite-coated components remained asymptomatic, with no wear or loosening. The uncoated components migrated after four years and three required revision. This trial shows good early results using a novel, hydroxyapatite-coated, physiological acetabular component.
Improvements in balance after total hip replacement
Authors: Majewski M. , Bischoff-Ferrari H. A. , Grüneberg C. , Dick W. , Allum J. H. J. 
Published: September 2005

We have investigated whether control of balance is improved during stance and gait and sit-to-stand tasks after unilateral total hip replacement undertaken for osteoarthritis of the hip. We examined 25 patients with a mean age of 67 years (sd 6.2) before and at four and 12 months after surgery and compared the findings with those of 50 healthy age-matched control subjects. For all tasks, balance was quantified using angular measurements of movement of the trunk. Before surgery, control of balance during gait and sit-to-stand tasks was abnormal in patients with severe osteoarthritis of the hip, while balance during stance was similar to that of the healthy control group. After total hip replacement, there was a progressive improvement at four and 12 months for most gait and sit-to-stand tasks and in the time needed to complete them. By 12 months, the values approached those of the control group. However, trunk pitch (forwards-backwards) and roll (side-to-side) velocities were less stable (greater than the control) when walking over barriers as was roll for the sit-to-stand task, indicative of a residual deficit of balance. Our data suggest that patients with symptomatic osteoarthritis of the hip have marked deficits of balance in gait tasks, which may explain the increased risk of falling which has been reported in some epidemiological studies. However, total hip replacement may help these patients to regain almost normal control of balance for some gait tasks, as we found in this study. Despite the improvement in most components of balance, however, the deficit in the control of trunk velocity during gait suggests that a cautious follow-up is required after total hip replacement regarding the risk of a fall, especially in the elderly.
Correction of rotational deformity of the tibia in cerebral palsy by percutaneous supramalleolar osteotomy
Authors: Inan M. , Ferri-de Baros F. , Chan G. , Dabney K. , Miller F. 
Published: September 2005

A percutaneous supramalleolar osteotomy with multiple drill holes and closed osteoclasis was used to correct rotational deformities of the tibia in patients with cerebral palsy. The technique is described and the results in 247 limbs (160 patients) are reported. The mean age at the time of surgery was 10.7 years (4 to 20). The radiographs were analysed for time to union, loss of correction, and angulation at the site of the osteotomy. Bone healing was obtained in all patients except one in a mean period of seven weeks (5 to 12). Malunion after loss of reduction at the site of the osteotomy developed in one tibia. Percutaneous supramalleolar osteotomy of the tibia is a safe and simple surgical procedure.
Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2
Authors: Huynh Thanh-Truc , Pacak Karel , Brouwers Frederieke M , Abu-Asab Mones S , Worrell Robert A , Walther MacClellan M , Elkahloun Abdel G , Goldstein David S , Cleary Susannah , Eisenhofer Graeme 
Published: September 2005

Objective: Phaeochromocytomas in patients with multiple endocrine neoplasia type 2 (MEN 2) produce adrenaline, whereas those with von Hippel-Lindau (VHL) syndrome do not. This study assessed whether these distinctions relate to differences in expression of the transporters responsible for uptake and storage of catecholamines – the noradrenaline transporter and the vesicular monoamine transporters (VMAT 1 and VMAT 2).
Methods: Tumour tissue and plasma samples were obtained from 31 patients with hereditary phaeochromocytoma − 18 with VHL syndrome and 13 with MEN 2. We used quantitative PCR, Western blotting, electron microscopy, immunohistochemistry and measurements of plasma and tumour catecholamines to assess differences in expression of the transporters in noradrenaline-producing vs adrenaline-producing hereditary tumours. These differences were compared with those in a further group of 26 patients with non-syndromic phaeochromocytoma.
Results: Adrenaline-producing phaeochromocytomas in MEN 2 patients expressed more noradrenaline transporter mRNA and protein than noradrenaline-producing tumours in VHL patients. In contrast, there was greater expression of VMAT 1 in VHL than MEN 2 tumours, while expression of VMAT 2 did not differ significantly. These differences were associated with larger numbers of storage vesicles and higher tissue contents of catecholamines in MEN 2 than in VHL tumours. Differences in expression of the noradrenaline transporter were weaker, and those of VMAT 1 and VMAT 2 stronger, in noradrenaline and adrenaline-producing non-syndromic than in hereditary tumours.
Conclusions: The findings show that, in addition to differences in catecholamine biosynthesis, phaeochromocytomas in MEN 2 and VHL syndrome also differ in expression of the transporters responsible for uptake and vesicular storage of catecholamines.
Differential expression of p160 steroid receptor coactivators in the rat testis and epididymis
Authors: Igarashi-Migitaka Junko , Takeshita Akira , Koibuchi Noriyuki , Yamada Shozo , Ohtani-Kaneko Ritsuko , Hirata Kazuaki 
Published: September 2005

Objective: Androgens are critical for the development and maintenance of male sexual characteristics. Their action is mediated through the androgen receptor (AR). Ligand-bound AR interacts with coactivator proteins that mediate transcriptional activation. Such coactivators include three members of the 160 kDa proteins (p160s): SRC-1, TIF2/GRIP1, and p/CIP/RAC3/ACTR/AIB1/TRAM-1. The aim of this study was to investigate the expression of the three p160 coactivators and their association with AR in testis and epididymis.Methods: We determined the localization of these three p160 coactivators in immature and mature rat testis, and epididymis by immunohistochemistry using the specific monoclonal antibodies. We also performed double immunofluorescence staining to examine whether p160s are colocalized with AR in these tissues.Results: In seminiferous tubules of mature rat testis, SRC-1 and TRAM-1 immunoreactivity was found predominantly in spermatogonia and spermatocytes. In contrast, TIF2 was expressed predominantly in Sertoli cells. AR was coexpressed with TIF2 in this cell type. In immature rat testis, however, all three coactivators were expressed in both germ cells and Sertoli cells. In the epididymis, SRC-1 and TIF2 immunoreactivities were localized in nuclei of epithelial cells. However, TRAM-1 immunostaining was observed in the luminal portion of the cytoplasm with greater intensity than in the nucleus, especially in the caput epididymidis.Conclusions: The cell-type-specific expression of p160 coactivators suggests specific roles in male reproductive organs. Further, the strong cytoplasmic localization of TRAM-1 protein in epithelial cells of epididymis suggests that TRAM-1 may have additional role(s) in transcriptional regulation.