bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of neovascularisation in the resolution of venous thrombus
Authors: Modarai Bijan , Guiver Burnand Kevin , Humphries Julia , Waltham Matthew , Smith Alberto 
Published: April 2005

SummaryDeep vein thrombosis (DVT) can give rise to chronic debilitating complications, which are expensive to treat. Anticoagulation, the standard therapy for DVT, prevents propagation, but does not remove the existing thrombus, which undergoes slow natural resolution. Alternative forms of treatment that accelerate resolution may arise from a better understanding of the cellular and molecular pathways that regulate the natural resolution of thrombi. This review will outline our current understanding of the mechanisms of thrombus resolution and the role of neovascularisation in this process. Novel experimental treatments that may one day find clinical use are also discussed. The process of thrombus resolution resembles wound healing. The mainly monocytic inflammatory infiltrate, which develops, is associated with the appearance of vascular channels. These cells may drive resolution by encouraging angiogenesis, which contributes to restoration of the vein lumen. Significant numbers of bone marrow-derived progenitor cells have also been found in naturally resolving thrombi, but their precise phenotype and their role in thrombus recanalisation is unclear. Enhanced thrombus neovascularisation and rapid vein recanalisation have been achieved in experimental models with proangiogenic agents. Recent reports of the role of bone marrow-derived progenitor cells in the revascularisation of ischaemic tissues suggest that it may be possible to obtain the same effect by delivering pluripotent or lineage specific stem cells into thrombus. These cells could contribute to thrombus recanalisation by expressing a variety of proangiogenic cytokines or by lining the new vessels that appear within the thrombus.
Phospholipid vesicles interfere with the binding of antibody fragments to the light chain of factor VIII
Authors: Lewis Deborah , Bovenschen Niels , Mertens Koen , Voorberg Jan , Ortel Thomas 
Published: April 2005

SummaryFactor VIII binds to phospholipid membranes through the C2 domain (S2173-Y2332). Residues M2199, F2200, L2251, L2252, V2223, W2313 and V2314 at the tips of β-hairpins and loops are thought to contribute to phospholipid membrane binding. Similarly, residues in the C2 domain of the homologous protein factor V form a phospholipid binding site, but residues in the A3 and C1 domains are also thought to contribute to membrane binding. Phage display technology was previously used to isolate factor VIII light chain specific single-chain variable domain fragments (scFv) from patients with factor VIII inhibitors. Phospholipid vesicles inhibited the binding of factor VIII to scFvsWR1 and WR16 (epitope: E2181-M2199) with half saturation values of 23 and 47 μM respectively. The single point mutant F2200A factor VIII light chain bound to WR1 and WR16 with a much lower affinity than wild type protein suggesting that residue F2200 is also included in the epitopes of these scFvs. Binding of factor VIII to C2-specific scFvsWR13 and EL14 (epitope: K2207-M2321) was not inhibited by phospholipid vesicles. Consistent with this, F2200A factor VIII light chain bound to these scFvs with the same affinity as the wild type protein. However, phospholipid vesicles also inhibited the binding of factor VIII to the A3-C1-specific scFvs KM36 (epitope: Q1778-D1840) and KM38 (epitope: S1690-N1777 and/or V1841-N2172) with half saturation values of 84 and 165 μM, respectively, suggesting that the A3 and/or C1 domains may contribute to membrane binding of the cofactor.
Opposite effects of CX3CR1 receptor polymorphisms V249I and T280M on the development of acute coronary syndrome
Authors: Haschemi Arvand , Endler Georg , Zorn Gerlinde , Weyand Cornelia , Maurer Gerald , Mannhalter Christine , Wojta Johann , Wagner Oswald , Huber Kurt , Niessner Alexander , Marculescu Rodrig 
Published: April 2005

SummarySeveral lines of evidence suggest that the chemokine fractalkine (FKN) and its receptor CX3CR1 contribute to the accumulation of leukocytes in the atherosclerotic plaque. The M280 allele of the CX3CR1T280M polymorphism modulates leukocyte recruitment and is associated with lower prevalence of cardiovascular disease. The influence of V249I, another CX3CR1 poly-morphism, is discussed controversially. We investigated the association of the alleles M280 and I249 of CX3CR1 with coronary artery disease (CAD) and with acute coronary syndrome (ACS). Additionally, we assessed their association with the soluble ligand FKN and inflammatory activation measured by high-sensitivity C-reactive protein (hsCRP). The genotypes of the V249I and T280M polymorphisms were determined in 1152 patients with suspected CAD. 720 (62.5%) individuals showed significant CAD with an ACS prevalence of 59.3%. Using multivariate regression, we found a harmful influence of I249 (adjusted OR=1.8, P<0.03) and a protective effect of M280 (adjusted OR=0.6, P<0.04) on the occurrence of ACS in patients with CAD. Correspondingly, patients with I249 but without M280 (17%) were at elevated risk of ACS (OR=1.6, P<0.04). During ACS these patients (carrying only I249) had significantly higher circulating concentrations of FKN and high sensitivity C-reactive protein (1.9– and 1.6-fold). We found no association of the I249 or the M280 allele with the occurrence of CAD. In conclusion, I249 and M280 have opposite effects on the occurrence of ACS. The presence of I249 not“balanced” by M280 confers an elevated risk of ACS. A FKN-mediated enhanced inflammatory activation might explain this increased risk.
Associations of fibrinogen and C-reactive protein with prevalent and incident coronary heart disease are attenuated by adjustment for confounding factors
Authors: Smith George , Rumley Ann , Lowe Gordon , Ebrahim Shah , Lawlor Debbie 
Published: April 2005

SummaryA cross sectional and prospective analysis of 3,745 British women aged 60–79 years at baseline was undertaken. Among these women there were 570 prevalent cases of coronary heart disease (CHD) and 151 new cases among 12,641 person-years of follow up of women who were free of CHD at baseline. Both fibrinogen and CRP were associated with indicators of socioeconomic position in childhood and adulthood and there was a cumulative effect of socioeconomic position from across the life course. The age-adjusted odds ratio (95% confidence interval) of prevalent CHD for a 1 unit (1 g/L) increase in fibrinogen was 1.29 (1.12, 1.49); with full adjustment for all potential confounding factors this attenuated to 1.09 (0.93, 1.28). The hazards ratio for incident CHD among those free of disease at baseline was 1.28 (1.00, 1.64); with full adjustment for all potential confounding factors this attenuated to 1.09 (0.84, 1.44). Similar effects of adjustment for confounding factors were seen for the associations between CRP and both prevalent and incident CHD. By contrast, the strong positive association between smoking (an established causal risk factor for CHD) and CHD was not attenuated by adjustment for life course socioeconomic position or other risk factors. We conclude that fibrinogen and CRP predict CHD but may not be causally related to it.
RNA interference in biology and disease
Authors: Sledz Carol A. , Williams Bryan R. G. 
Published: April 2005

Abstract
RNA interference (RNAi) is a conserved biologic response to double-stranded RNA that results in the sequence-specific silencing of target gene expression. Over the past 5 years, an intensive research effort has facilitated the rapid movement of RNAi from a relatively obscure biologic phenomenon to a valuable tool used to silence target gene expression and perform large-scale functional genomic screens. In fact, recent studies reported in this journal and others have demonstrated success using RNAi to address the role of oncogene expression in leukemia cell lines and to validate the therapeutic potential of RNAi for treating these blood disorders. In order to advance these applications and gain an appreciation for the future of RNAi both in basic research and in the treatment of diseases caused by aberrant gene expression, it is important to have an understanding of the process of RNAi and its limitations.
Lipoprotein docosapentaenoic acid is associated with serum matrix metalloproteinase-9 concentration
Authors: Solakivi Tiina , Jaakkola Olli , Kalela Anne , Pispa Mari , Salomäki Anne , Lehtimäki Terho , Höyhtyä Matti , Jokela Hannu , Nikkari Seppo T 
Published: April 2005

Abstract

Background
Polyunsaturated fatty acids (PUFA) are thought to play important roles in inflammation. The n-3 series is considered as anti-inflammatory, and some studies have reported increased plasma n-3 polyunsaturated fatty acid pattern in chronic inflammatory conditions. In this study we sought to clarify relationships of the levels of arachidonic acid and the polyunsaturated n-3 fatty acid compositions of isolated LDL, HDL2 and HDL3 particles with matrix metalloproteinase-9 (MMP-9), a marker of inflammation.

Results
The subjects were divided into two groups: those with lower and those with higher than the median serum MMP-9 concentration. In all lipoprotein fractions, the mean percentage of docosapentaenoic acid (C22:5n-3) was higher in the group of subjects with higher MMP-9 level than in those with lower serum MMP-9 concentration (P < 0.01 for all). Likewise, the ratio of docosapentaenoic acid to arachidonic acid (C20:4n-6) was higher in the subjects with higher MMP-9 compared with the lower MMP-9 group (P < 0.001 for all).

Conclusion
So far, the evidence for an anti-inflammatory role of the n-3 PUFA has come from dietary interventions. Our results were obtained from a free-living population and indicate that there is a positive correlation between n-3 docosapentaenoic acid and MMP-9. What had triggered the rise in MMP-9 is not known, since serum level of MMP-9 is raised in many inflammatory conditions. These findings may indicate an increased biosynthesis of n-3 polyunsaturated fatty acids in subclinical inflammation.
The biopsychosocial model and hypothyroidism
Authors: Brown Benjamin T , Bonello Rod , Pollard Henry 
Published: April 2005

AbstractThis paper comments on the role and emergence of the biopsychosocial model in modern medical literature and health care settings. The evolution of the biopsychosocial model and its close association with modern pain theory is also examined. This paper seeks to discuss the place of this model with respect to the management of hypothyroidism. This discussion represents a forerunner to a randomised control trial that will seek to investigate the effect of a biopsychosocial-based treatment regime on hypothyroidism.
Inhaled Insulin: Exubera
Authors: Odegard Peggy Soule , Capoccia Kam L 
Published: April 2005

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of Exubera, a novel, dry-powder formulation of insulin for inhalation, and describe patient satisfaction and quality-of-life data. DATA SOURCES: A MEDLINE search (1966–November 2004) was conducted using the key words inhaled insulin and Exubera for clinical trials limited to human research published in English. BIOSIS Previews and the American Diabetes Association Scientific Abstracts were used for published abstract information. STUDY SELECTION AND DATA EXTRACTION: All available human studies of Exubera were selected for review. References of identified articles were used for additional citations. DATA SYNTHESIS: Exubera is a rapid-acting insulin administered by oral inhalation before meals with long-acting insulin administered subcutaneously once or twice daily for type 1 or 2 diabetes mellitus. Exubera provides similar efficacy and improved patient satisfaction compared with standard subcutaneous insulin therapy (ie, NPH twice daily with regular insulin before meals). Efficacy has also been demonstrated for Exubera when used as adjunctive therapy with oral medications for type 2 diabetes. The onset of Exubera is more rapid and its duration of action is similar to that of regular insulin. To date, Exubera administered before meals with a once-daily long-acting subcutaneous insulin (usually Ultralente) has been compared with standard subcutaneous NPH/regular insulin regimens. Comparison of premeal Exubera plus a basal long-acting insulin analog (eg, glargine) with a regimen of premeal subcutaneous rapid-acting insulin analog (eg, lispro or aspart) plus a basal long-acting insulin analog (eg, glargine) is needed to fully evaluate Exubera. Pulmonary safety appears to be maintained for up to 4 years, although there are no data, as of this writing, on the use of this agent in patients with pulmonary conditions. CONCLUSIONS: Exubera is an effective inhaled insulin for preprandial use in type 1 or 2 diabetes. Improved patient satisfaction over injected insulin increases its potential for use earlier in the treatment of type 2 diabetes.
A New Pyridine‐2,6‐bis(oxazoline) for Efficient and Flexible Lanthanide‐Based Catalysts of Enantioselective Reactions with 3‐Alkenoyl‐2‐oxazolidinones
Authors: Desimoni Giovanni , Faita Giuseppe , Guala Matilde , Laurenti Anna , Mella Mariella 
Published: April 2005

AbstractA new pyridine‐2,6‐bis(oxazoline) (4) has been easily synthesised from the reaction of (1S,2S)‐2‐amino‐1‐phenylpropane‐1,3‐diol (1) and dimethyl pyridine‐2,6‐dicarboximidate (2), followed by TIPS (TIPS=triisopropylsilyl) protection of the 4′‐CH2OH group. The catalysts derived from 4 and eight lanthanide(III) triflates have been tested over three reactions involving 3‐acryloyl‐ and 3‐crotonoyloxazolidinones (5 a,b): the Diels–Alder (DA) reaction with cyclopentadiene, the 1,3‐dipolar cycloaddition with diphenyl nitrone and the Mukaiyama–Michael reaction with 2‐trimethylsilyloxyfuran. Several reactions exhibit very good enantioselectivity (ee>90 %), and the opposite enantiomers can be easily obtained simply by changing the cation. This specific feature of the ligand can be appreciated in the DA reaction of 5 a, since the catalyst [ScIII(4)] gives the adduct (2′S)‐9 a with 99 % ee, whereas the catalyst [YIII(4)] gives the opposite enantiomer with 95 % ee. A rationale of the enantioselectivity is proposed on the basis of the NMR spectra of La‐based complexes involving 4 and 5 as ligands.
Versatile Glycoblotting Nanoparticles for High‐Throughput Protein Glycomics
Authors: Niikura Kenichi , Kamitani Ryosuke , Kurogochi Masaki , Uematsu Rie , Shinohara Yasuro , Nakagawa Hiroaki , Deguchi Kisaburo , Monde Kenji , Kondo Hirosato , Nishimura Shin‐Ichiro 
Published: April 2005

AbstractWe have developed an effective and practical trap‐and‐release method based on chemoselective ligation of carbohydrates with reactive aminooxyl groups attached to the surface of nanoparticles (referred to as glycoblotting nanoparticles). These glycoblotting nanoparticles were synthesized by UV irradiation of diacetylene‐functionalized lipids that contain the aminooxyl group. The glycoblotting nanoparticles captured carbohydrates in aqueous solution under mild conditions and were collected by simple centrifugation. The trapped carbohydrates were effectively released from the nanoparticles under acidic conditions to give pure oligosaccharides. This glycoblotting process reduced the time required for the purification process of carbohydrates to less than 6 h, compared to the several days needed for conventional chromatographic techniques. The oligosaccharides (N‐glycan) were released from ovalbumin (glycoprotein) by PNGase F after tryptic digestion. MALDI‐TOF mass spectra before purification did not show any significant signals corresponding to N‐glycans because these signals were hidden by the large signals of the abundant peptides. However, after purification with the glycoblotting nanoparticles, only signals corresponding to oligosaccharides appeared. We also demonstrated a clear analysis of the oligosaccharides contained in the mice dermis by means of glycoblotting.
Excitation‐Energy Migration in Self‐Assembled Cyclic Zinc(II)–Porphyrin Arrays: A Close Mimicry of a Natural Light‐Harvesting System
Authors: Hwang In‐Wook , Park Mira , Ahn Tae Kyu , Yoon Zin Seok , Ko Dah Mee , Kim Dongho , Ito Fuyuki , Ishibashi Yukihide , Khan Sazzadur R. , Nagasawa Yutaka , Miyasaka Hiroshi , Ikeda Chusaku , Takahashi Ryoichi , Ogawa Kazuya , Satake Akiharu , Kobuke Yoshiaki 
Published: April 2005

AbstractThe excitation‐energy‐hopping (EEH) times within two‐dimensional cyclic zinc(II)–porphyrin arrays 5 and 6, which were prepared by intermolecular coordination and ring‐closing metathesis reaction of olefins, were deduced by modeling the EEH process based on the anisotropy depolarization as well as the exciton–exciton annihilation dynamics. Assuming the number of energy‐hopping sites N=5 and 6, the two different experimental observables, that is, anisotropy depolarization and exciton–excition annihilation times, consistently give the EEH times of 8.0±0.5 and 5.3±0.6 ps through the 1,3‐phenylene linkages of 5 and 6, respectively. Accordingly, the self‐assembled cyclic porphyrin arrays have proven to be well‐defined two‐dimensional models for natural light‐harvesting complexes.
Synthesis of enantiopure phthalides including 3‐butylphthalide, a fragrance component of celery oil, and determination of their absolute configurations
Authors: Kosaka Masashi , Sekiguchi Satoshi , Naito Junpei , Uemura Makoto , Kuwahara Shunsuke , Watanabe Masataka , Harada Nobuyuki , Hiroi Kunio 
Published: April 2005

AbstractEnantiopure phthalides 2 and 5–8 were synthesized via enantioresolution of the corresponding alcohols with a chiral auxiliary of camphorsultam dichlorophthalic acid, (1S,2R,4R)‐(−)‐CSDP acid 3, followed by solvolysis with KOH in MeOH and the catalytic oxidation of chiral glycols with iridium complex 28. The absolute configurations of phthalides 2 and 5–8 were determined by applying the 1H‐NMR anisotropy method of MαNP acid (4), 2‐methoxy‐2‐(1‐naphthyl)propionic acid, to the chiral synthetic precursory alcohols. In the case of 3‐phenylphthalide (R)‐(−)‐7, the absolute configuration determined by the 1H‐NMR anisotropy method using MαNP acid 4 agreed with that by the X‐ray crystallographic method. By applying these methods, 3‐butylphthalide (S)‐(−)‐2, a fragrance component of essential oil of celery, has been synthesized in an enantiopure form, and its absolute configuration was unambiguously determined. Chirality 17:218–232, 2005. © 2005 Wiley‐Liss, Inc.
Management of suspicious or indeterminate calcifications and impact on local control
Authors: Lally Brian E. , Haffty Bruce G. , Moran Meena S. , Colasanto Joseph M. , Higgins Susan A. 
Published: April 2005

AbstractBACKGROUNDThe current study was undertaken to determine the potential advantage associated with complete removal of suspicious or indeterminate calcifications (SIC) before the initiation of irradiation as part of breast conservation therapy (BCT).METHODSOf 2045 patients treated with BCT at Yale University School of Medicine (New Haven, Connecticut) and satellite facilities before 2002, 111 women, included 3 patients with bilateral disease, had a postexcision preirradiation mammogram (PREMAMMO) to evaluate residual SIC. Thus, 114 breasts were at risk for local disease recurrence. Seventy‐five breasts at risk had no residual SIC and proceeded to undergo radiotherapy (XRT) without further surgery or mammography. Of the remaining 39 breasts at risk, only 3 underwent a PREMAMMO with documented removal of all calcifications (DRC). Thirty‐six breasts at risk proceeded to XRT with either known SIC or with nondocumented removal of calcifications (NDRC) after another excision.RESULTSOf the 78 breasts at risk with DRC via PREMAMMO, there were 7 local failures (LF) and 1 distant failure. Of the 36 breasts with NDRC via PREMAMMO, there were 7 LF and 1 regional failure. Of the 34 breasts who underwent reexcision after detection of SIC by PREMAMMO, 20 (59%) were found to have residual disease.CONCLUSIONSPatients with DRC were found to have better local control than patients with NDRC. In addition, the presence of SIC on a PREMAMMO was associated with a high probability of detecting residual disease. Cancer 2005. © 2005 American Cancer Society.
Factors affecting bone mineral density in patients with prostate carcinoma before and after orchidectomy
Authors: Agarwal Mayank M. , Khandelwal Niranjan , Mandal Arup K. , Rana Satyawati V. , Gupta Vivek , Chandra Mohan Vaddi , Kishore Gottapu V. M. K. 
Published: April 2005

AbstractBACKGROUNDOrchidectomy is an accepted form of androgen‐deprivation therapy (ADT) for prostate carcinoma. Osteoporosis is common in elderly individuals and is accelerated by ADT. The authors studied changes in bone mineral density (BMD) after ADT and factors that affected those changes.METHODSFifty patients with prostatic adenocarcinoma who opted to undergo orchidectomy were studied prospectively. All patients completed 6 months of follow‐up, and 20 of those patients completed 12 months of follow‐up. Patients' age, weight, height, body mass index (BMI), physical activity, addiction (smoking, alcohol), dietary calcium intake, and lactose tolerance status were noted. Lumbar spinal (L1–L3) trabecular BMD was measured with quantitative computed tomography (QCT) at baseline and every 6 months for 1 year and was compared with preoperative values. The effects of various patient characteristics on preoperative BMD and changes in BMD also were analyzed.RESULTSThe mean ± standard deviation (SD) age of the patients was 69.5 ± 8.1 years, BMI was 23.5 ± 3.9 kg/m2, dietary calcium intake was 1066.1 ± 443.3 mg per day. Thirty‐eight percent of patients were lactose intolerant. Sixty‐two percent of patients were in the light weight‐bearing activity group. The mean ± SD preoperative BMD was 119.2 ± 34.9 mg/cc, with T‐scores of − 1.77 ± 1.22 and Z‐scores of 0.43 ± 1.27. A decrease in BMD during the first 6 months (≈ 13%) was statistically significant (P = 0.0001) and continued further during next 6 months (BMD loss of ≈ 18% at 12 months). Patients with osteoporosis, as defined by T‐scores ≤ − 2.5, increased from 24% at baseline to 48% at 6 months. Nonsmokers, nonalcoholics, patients with higher physical activity, and patients with a BMI > 25 kg/m2 had statistically significant higher BMD compared with their counterparts (P < 0.05). Body weight < 60 kg and BMI < 25 kg/m2 were significant risk factors for loss of BMD (P < 0.05). Dietary calcium had a discernible but statistically insignificant effect on BMD (P = 0.16). Lactose intolerance had no significant effect on BMD or bone loss.CONCLUSIONSOsteoporosis was common in the population affected by prostate carcinoma. Orchidectomy led to accelerated bone loss. Periodic measurement of BMD after ADT would help in the early detection of osteoporosis. Maintenance of high BMI, weight‐bearing physical activity, avoidance of alcohol and smoking, and possibly high dietary calcium intake help in maintaining bone mass. Cancer 2005. © 2005 American Cancer Society.