bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural gene therapy in monozygotic twins with Fanconi anemia
Authors: Mankad Anuj , Taniguchi Toshiyasu , Cox Barbara , Akkari Yassmine , Rathbun R. Keaney , Lucas Lora , Bagby Grover , Olson Susan , D'Andrea Alan , Grompe Markus 
Published: January 2006

Abstract
Monozygotic twin sisters, with nonhematologic symptoms of Fanconi anemia (FA), were discovered to be somatic mosaics for mutations in the FANCA gene. Skin fibroblasts, but not lymphocytes or committed hematopoietic progenitors, were sensitive to DNA cross-linking agents. Molecular analysis revealed, in skin cells of both twins, a frameshift causing deletion in exon 27 (2555ΔT) and an exon 28 missense mutation (2670G>A/R880Q). The latter resulted in primarily cytoplasmic expression and reduced function of the mutant FANCA (R880Q) protein. Surprisingly, the same acquired exon 30 missense change (2927G>A/E966K) was detected in the hematopoietic cells of both sisters, but not in their fibroblasts, nor in either parent. This compensatory mutation existed in cis with the maternal exon 28 mutation, and it restored function and nuclear localization of the resulting protein. Both sisters have been free of hematologic symptoms for more than 2 decades, suggesting that this de novo mutation occurred prenatally in a single hematopoietic stem cell (HSC) in one twin and that descendants of this functionally corrected HSC, via intra-uterine circulation, repopulated the blood lineages of both sisters. This finding suggests that treating FA patients with gene therapy might require transduction of only a few hematopoietic stem cells.
Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation
Authors: Dispenzieri Angela , Lacy Martha Q. , Katzmann Jerry A. , Rajkumar S. Vincent , Abraham Roshini S. , Hayman Suzanne R. , Kumar Shaji K. , Clark Raynell , Kyle Robert A. , Litzow Mark R. , Inwards David J. , Ansell Stephen M. , Micallef Ivana M. , Porrata Luis F. , Elliott Michelle A. , Johnston Patrick B. , Greipp Philip R. , Witzig Thomas E. , Zeldenrust Steven R. , Russell Stephen J. , Gastineau Dennis , Gertz Morie A. 
Published: January 2006

AbstractThe immunoglobulin free light chain (FLC) is the precursor protein of amyloid in primary systemic amyloidosis (AL). Historically, the ability to monitor the amyloid protein precursor protein has been crude. We evaluated the utility of the FLC assay in a retrospective analysis of patients with AL undergoing peripheral blood stem cell transplantation (PBSCT). Ninety-three such patients had serial FLC measurements performed. The prognostic effects of the initial concentration and the extent of reduction of monoclonal FLC on survival were studied. There was a significantly higher risk of death in patients with higher baseline FLC (hazard ratio 2.6, P < .04). Baseline FLC correlated with serum cardiac troponin levels, and higher FLC levels were associated with more organs involved by amyloid, suggesting that high FLC levels may be associated with more advanced disease. The percent FLC reduction did not predict for survival, but the absolute level of FLC achieved after therapy did. Normalization of FLC level after PBSCT predicted for both organ response and complete hematologic response. Achievement of FLC response was a better predictor of survival than achievement of complete hematologic response or normalization of the FLC ratio. FLC measurements both before and after PBSCT are important predictors of patient outcome.
Mutation of mouse Mayp/Pstpip2 causes a macrophage autoinflammatory disease
Authors: Grosse Johannes , Chitu Violeta , Marquardt Andreas , Hanke Petra , Schmittwolf Carolin , Zeitlmann Lutz , Schropp Patricia , Barth Bettina , Yu Philipp , Paffenholz Rainer , Stumm Gabriele , Nehls Michael , Stanley E. Richard 
Published: January 2006

AbstractMacrophage actin-associated tyrosine phosphorylated protein (MAYP)/PSTPIP2, a PCH protein, is involved in the regulation of macrophage motility. Mutations in a closely related gene, PSTPIP1/CD2BP1, cause a dominantly inherited autoinflammatory disorder known as PAPA syndrome. A mutant mouse obtained by chemical mutagenesis exhibited an autoinflammatory disorder characterized by macrophage infiltration and inflammation, leading to osteolysis and necrosis in paws and necrosis of ears. Positional cloning of this recessive mutation, termed Lupo, identified a T to A nucleotide exchange leading to an amino acid substitution (I282N) in the sequence of MAYP. MaypLp/Lp disease was transferable by bone marrow transplantation and developed in the absence of lymphocytes. Consistent with the involvement of macrophages, lesion development could be prevented by the administration of clodronate liposomes. MAYP is expressed in monocytes/macrophages and in a Mac1+ subfraction of granulocytes. LPS stimulation increases its expression in macrophages. Because of the instability of the mutant protein, MAYP expression is reduced 3-fold in MaypLp/Lp macrophages and, on LPS stimulation, does not rise above the level of unstimulated wild-type (WT) cells. MaypLp/Lp mice expressed elevated circulating levels of several cytokines, including MCP-1; their macrophages exhibited altered cytokine production in vitro. These studies suggest that MAYP plays an anti-inflammatory role in macrophages.
Thrombophilic abnormalities, oral contraceptives, and risk of cerebral vein thrombosis: a meta-analysis
Authors: Dentali Francesco , Crowther Mark , Ageno Walter 
Published: January 2006

AbstractRecent studies suggest that thrombophilic abnormalities and the use of oral contraceptives (OCs) are the leading causes of cerebral vein thrombosis (CVT). The purpose of this study was to assess the association between CVT and thrombophilic states, OCs, and their interaction. For data sources, we used the MEDLINE, EMBASE, and Cochrane Library databases (January 1994 to March 2005), reference lists of retrieved articles, and contact with content experts. We selected studies comparing the prevalence of OC use and the prevalence of prothrombitic abnormalities in patients with CVT compared with healthy controls. Two reviewers independently selected studies and extracted study characteristics, quality, and outcomes. Odds ratios (ORs) were calculated for each trial and pooled using the Mantel-Haenszel method. Seventeen studies were included. There was an increased risk of CVT in patients using OCs (OR 5.59; 95% confidence interval [CI] 3.95 to 7.91; P < .001), and in patients with factor V Leiden (OR 3.38; 95% CI 2.27 to 5.05; P < .001), with mutation G20 210A of prothrombin (OR 9.27; 95% CI 5.85 to 14.67; P < .001) and with hyperhomocysteinemia (OR 4.07; 95% CI 2.54 to 6.52; P < .001). We concluded that OC users, and patients with factor V Leiden, the prothrombin G20 120A mutation, and hyperhomocysteinemia are at a significantly increased risk of CVT.
MED220/Thyroid Receptor-Associated Protein 220 Functions as a Transcriptional Coactivator with Pit-1 and GATA-2 on the Thyrotropin-β Promoter in Thyrotropes
Authors: Gordon David F. , Tucker Elizabeth A. , Tundwal Kavita , Hall Heather , Wood William M. , Ridgway E. C. 
Published: January 2006

AbstractMediator (MED) 220/thyroid receptor-associated protein (TRAP) 220 is a transcriptional mediator that interacts with liganded thyroid/steroid hormone receptors. MED220 haploinsufficient heterozygotes exhibited hypothyroidism and reduced TSHβ transcripts, suggesting a specific function for TSHβ transcription. We previously demonstrated that Pit-1 and GATA-2 can bind to a composite element within the proximal TSHβ promoter and synergistically activate transcription. We detected MED220 expression in TtT-97 thyrotropes by Northern and Western blot analysis. Cotransfections in CV-1 cells showed that Pit-1, GATA-2, or MED220 alone did not markedly stimulate the TSHβ promoter. However, Pit-1 plus GATA-2 resulted in an 10-fold activation, demonstrating synergistic cooperativity. Titration of MED220 resulted in a further dose-dependent stimulation up to 25-fold that was promoter specific. Glutathione-S-transferase interaction studies showed that MED220 or GATA-2 each bound the homeodomain of Pit-1, whereas MED220 interacted independently with each zinc finger of GATA-2 but not with either terminus. MED220 interacted with GATA-2 and Pit-1 over a broad region of its N terminus. These regions of interaction were also important for maximal function. Coimmunoprecipitation confirmed that all three factors can interact in thyrotropes and chromatin immunoprecipitation demonstrated in vivo occupancy on the proximal TSHβ promoter. Thus, the TSHβ gene is maximally activated by a combination of three thyrotrope transcription factors that act via both protein-DNA and protein-protein interactions.
Contribution of The Annals Of Pharmacotherapy to the Development of Clinical Pharmacy
Authors: McLeod Donald C 
Published: January 2006

2006 marks the 40th year of publication for The Annals. Over that time, The Annals has been an important contributor to the development of clinical pharmacy, with the journal's founder and first editor, Dr. Don E Francke, exerting a profound influence on the evolution of the profession of pharmacy. Throughout 2006, we will publish articles authored by practitioners, including those pioneering clinical pharmacy, as well as those who have more recently entered the profession and a well-established specialty. Donald C McLeod, the first chairman of the Editorial Board for The Annals, presents the initial article of the series in this issue. Edward Hartshorn, one of the first to recognize the significant impact of drug interactions on pharmacotherapy, also offers his memories of the early days of the journal and how clinical pharmacy has grown (see page 112). In addition, we are also presenting editorials from the early history of The Annals that have given direction and shape to the practice of clinical pharmacy (see pages 114-22).
Coelution of Other Proteins with Albumin during Size-Exclusion HPLC: Implications for Analysis of Urinary Albumin
Authors: Sviridov Denis , Meilinger Bonnie , Drake Steven K , Hoehn Gerard T , Hortin Glen L 
Published: January 2006

AbstractBackground: Size-exclusion HPLC has been used as an alternative to immunoassays for quantifying urinary albumin (microalbumin). Systematically higher values for the HPLC method have been proposed to result from nonimmunoreactive albumin.Methods: We evaluated separation of purified proteins and urinary components by size-exclusion HPLC using a Zorbax Bio Series GF-250 column eluted with phosphate-buffered saline. Urinary components eluting in the “albumin” peak were analyzed by mass spectrometry and reversed-phase HPLC.Results: Several proteins, such as transferrin, α1-proteinase inhibitor, α1-acid glycoprotein, and α2-HS glycoprotein, analyzed as purified components, were not resolved from albumin by size-exclusion HPLC. Peaks for other proteins, such as IgG and urinary components identified as dimers of α1-microglobulin and immunoglobulin light chains, overlapped with the albumin peak. Profiles of urine specimens showed variable amounts of components overlapping with albumin. Furthermore, the albumin peak obtained by size-exclusion HPLC was found by mass spectrometry and reversed-phase HPLC to contain multiple components in addition to albumin.Conclusions: Size-exclusion HPLC does not resolve albumin from several other proteins in urine. The albumin peak resolved by this technique, although predominantly composed of albumin, contains several coeluting globulins that would contribute to overestimation of albumin concentration by size-exclusion HPLC.
Allelic Losses of Chromosome 10 in Glioma Tissues Detected by Quantitative Single-Strand Conformation Polymorphism Analysis
Authors: Hata Nobuhiro , Yoshimoto Koji , Yokoyama Nobuhiko , Mizoguchi Masahiro , Shono Tadahisa , Guan Yanlei , Tahira Tomoko , Kukita Yoji , Higasa Koichiro , Nagata Shinji , Iwaki Toru , Sasaki Tomio , Hayashi Kenshi 
Published: January 2006

Abstract
Background: Detection of loss of heterozygosity (LOH) in clinical tissue samples is frequently difficult because samples are usually contaminated with noncancerous cells or because tumor cells in single tissues have genetic heterogeneity, and the precision of available techniques is insufficient for reliable analysis in such materials. We hypothesized that single-strand conformation polymorphism (SSCP) analysis can precisely quantify the gene dosage in mixed samples and is suitable for detection of LOH in clinical tissue samples.
Methods: We assessed the accuracy of a fluorescent SSCP method for the quantification of single-nucleotide polymorphism (SNP) alleles, using DNAs that were composed of cancerous DNA mixed with noncancerous DNA at various ratios. We applied this method to precisely characterize LOH in glioma tissue samples, using 96 SNPs that were evenly distributed throughout chromosome 10.
Results: LOH could be detected even in the cancerous DNA heavily contaminated (up to 80%) with noncancerous DNA. Using this method, we obtained LOH profiles of 56 gliomas with resolution at the SNP level (i.e., 1.5-Mbp interval). Anaplastic astrocytomas exhibited both 10p and 10q LOH, whereas diffuse astrocytomas frequently (63% of the cases) exhibited loss of 10p alone. We also found a possible new LOH region (around 10p13) in gliomas.
Conclusions: The present method is effective for precise mapping of LOH region in surgically obtained tumor tissues and could be applicable to the genetic diagnosis of cancers other than gliomas.
Changes in Nasorespiratory Function in Association with Maxillary Distraction Osteogenesis in Subjects with Cleft Lip and Palate
Authors: Saito Kiyo , Ono Takashi , Mochida Masumi , Ohyama Kimie 
Published: January 2006

Objective The current study aimed to determine how nasorespiratory function changes in association with maxillary distraction osteogenesis (DO). Furthermore, with regard to impaired nasorespiratory function, the possibility of a relationship between the cleft side and laterality and any effect of maxillary distraction osteogenesis was investigated. Design In this descriptive, prospective clinical report, subjective and objective data regarding nasorespiratory function before and after maxillary distraction osteogenesis were compared. Subjects Data from 13 subjects with cleft lip and palate were used. Subjects had a severe maxillary deficiency and underwent distraction osteogenesis using a rigid external device system. Outcome Measures The subjective measure was the score on a questionnaire regarding nasorespiratory function using a visual analog scale. The objective measure was nasal resistance. Results The visual analog scale score for two items significantly decreased just after distraction osteogenesis. Nasal resistance also significantly decreased 1 year after distraction osteogenesis. Moreover, nasal resistance on the cleft side was significantly greater than that on the noncleft side just before and 1 year after distraction osteogenesis. There was a significant positive correlation between changes in the visual analog scale score and nasal resistance. Conclusions These results suggest that nasorespiratory function changes in association with maxillary distraction osteogenesis in subjects with cleft lip and palate. Moreover, it appears that nasal obstruction on the cleft side does not change in subjects with unilateral cleft lip and palate.
A Pharyngeal and Ectopic Hypophysis in a Neonate with Craniofacial Abnormalities: A Case Report and Review of Development and Structure
Authors: Osman Mohseena , Allan J. C. , Kramer Beverley 
Published: January 2006

Objective A large excrescence was found bulging from the mucoperiosteum of the nasopharynx in a neonate displaying abnormal craniofacial features. The aim of this study was to determine the nature of this tissue mass. Design Histological examination of this mass of tissue and the surrounding nasopharyngeal mucosal tissue, as well as tissue located in the sella turcica of the sphenoid bone, were carried out. In addition, tissue in a canal connecting the large mass to the sella turcica was removed for analysis. Results Nervous elements and adenohypophyseal tissue were histologically identified in the large excrescence, but were separate from adenohypophyseal tissue of the pharyngeal hypophysis. Both structures were located in the mucoperiosteum of the nasopharynx. Conclusions The large tissue mass found in the nasopharynx is histologically identical to a sellar hypophyseal gland, but differed from the adjacent pharyngeal hypophysis in histological composition. The mass, although sellar in nature, however, was placed ectopically in the nasopharynx and is hence termed pharyngosellar to indicate its abnormal position, as well as its origin.
Management of the Prominent Premaxilla in Bilateral Cleft Lip and Palate
Authors: Aburezq Hisham , Daskalogiannakis John , Forrest Christopher 
Published: January 2006

Design and Objective This study was designed to present our philosophy in managing the prominent premaxilla in patients with bilateral cleft lip and palate. Indications, contraindications, and the pre- and postoperative orthodontic role are defined. Setting Tertiary care, cleft palate and craniofacial center—academic institution. Patients Under review were four cases of bilateral cleft lip and palate presenting with prominent premaxilla and operated on by a single surgeon between 1996 and 2004. Conclusion With appropriate patient selection, bilateral alveolar bone grafting with premaxillary repositioning is a safe procedure and can produce good aesthetic and functional results.
A Therapeutic Camp Weekend for Adolescents with Craniofacial Differences
Authors: Tiemens Kim , Beveridge Heather L. , Nicholas David B. 
Published: January 2006

Objective A therapeutic camp weekend was developed for adolescents living with a facial difference. The camp comprised a program that involved personal challenges and group-building activities, as well as social recreational activities. This article outlines the camp intervention, with recommendations for future camp evaluation.
Both Nasal Cerebral Heterotopia and Encephalocele in the Same Patient
Authors: Fujioka Masaki , Tasaki Isao , Nakayama Riko , Yakabe Aya , Baba Hiroshi , Toda Keisuke , Itoh Masahiro , Hirano Akiyoshi 
Published: January 2006

Objective and Patient Both nasal cerebral heterotopia and encephalocele are rare congenital benign masses of neurogenic origin caused by an embryonic developmental abnormality. It is generally accepted that nasal heterotopia is a sequelae to encephalocele. This report presents an unusual case of nasal cerebral heterotopia and encephalocele arising in the same patient. The patient had a firm, solid mass measuring 1.5 × 1.0 cm on the bridge of the nose covered with normal skin and another mass in the nasal cavity obstructing the right nasal cavity. Computed tomography (CT) demonstrated that the nasal bone separated these masses. CT also showed a bony defect at the skull base. Surgery consisted of dividing the encephalocele and closure of the skull base fistulae, along with nasal subcutaneous mass enucleation. Results Intraoperative examination indicated the existence of a pit on the nasal bone where the pedicle of the nasal subcutaneous mass connected. Microscopic examination of the nasal cavity mass demonstrated meningoencephalocele, and examination of the nasal subcutaneous mass demonstrated nasal cerebral heterotopia, which was confirmed by immunohistochemical staining. After 10 months, complete removal of the subcutaneous nasal mass was recognized and there was no evidence of recurrence. Conclusion Findings in this case suggest that the nasal cerebral heterotopias will result from encephalocele.
Five-Year Experience Comparing Resorbable to Titanium Miniplate Osteosynthesis in Cleft Lip and Palate Orthognathic Surgery
Authors: Landes Constantin A. , Ballon Alexander 
Published: January 2006

Objective To evaluate 5-year outcome stability and complications in orthognathic surgery using resorbable versus titanium osteofixation. Patients, Methods Twenty-two cleft lip and palate maxillary retrognathia cases were operated on using either poly (70L-lactide-co-30DL-lactide) or titanium miniplate osteofixation. All had two-piece Le Fort I maxillary advancement osteotomy, 11 had simultaneous mandibular setback, and 13 had alveolar bone grafts. Results Average operative movement and postoperative instability recorded for maxillary horizontal movement (A-point-Nasion) were 2.5 mm and 2.1 mm for the study group, compared with 6.3 mm and 1.9 mm for the control group. For maxillary vertical movement (ANS-Nasion), measured values were 4.9 and 1.3 mm for the study group and 2.3 and 0.9 mm for the controls. For mandibular horizontal movement, measured values were 10.7 mm and 2.8 mm for the study group and 1.9 mm and 0.8 mm for the controls. Gonial angle measures were 7.1° and 3.5° for the study group and 6.7° and 3.1° for the controls. Foreign body granuloma and fistulation occurred in 1 (9%) member of the study group, but was treated successfully with debridement; implant palpability subsided after 24 months. Three (27%) controls required plate removal, but the remaining plates were palpable. Conclusion In the study group, horizontal maxillary stability appeared inferior to vertical stability, but mandibular stability was more reliable. Because groups were not matched for magnitude or direction of movement, the results of this study are preliminary and should be interpreted cautiously.
Assessing the responses of creek chub (Semotilus atromaculatus) and pearl dace (Semotilus margarita) to metal mine effluents using in situ artificial streams in Sudbury, Ontario, Canada
Authors: Dubé Monique G. , MacLatchy Deborah L. , Hruska Kimberly A. , Glozier Nancy E. 
Published: January 2006

AbstractMining of the world's second-largest nickel deposits in the area of Sudbury, Ontario, Canada, has caused acidification and metal saturation of some catchments. We conducted artificial stream studies in the years 2001 and 2002 to assess the effects of treated metal mine effluents (MMEs) from three different mining operations discharging to Junction Creek, Sudbury, on two fish species, creek chub (Semotilus atromaculatus) and pearl dace (Semotilus margarita). Treatments tested for 35 to 41 d included reference water, Garson MME (30%), Nolin MME (20%), and Copper Cliff MME (45%). In 2001, effects on chub included reduced survival and depressed testosterone levels (fivefold reduction) after exposure to all MMEs. In 2002, chub and dace survival were reduced to less than 60% in the Copper Cliff and Garson treatments. In addition, the total body weights of male and female dace were reduced after exposure to the Garson and Copper Cliff treatments. In 2001 and 2002, responses were most common to the 45% Copper Cliff and 30% Garson effluents, with consistent increases in nickel, rubidium, strontium, iron, lithium, thallium, and selenium observed across treatment waters and body tissues. More work is required to link observed effects to field effects and to identify multitrophic level responses of the ecosystem to the MMEs. The artificial stream studies provided a mechanism to identify changes in the endpoints of relevant fish species exposed to present-day metal mine discharges independent of historical depositions of metals in the Sudbury area.