bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized double-blind controlled trial of roxithromycin for prevention of abdominal aortic aneurysm expansion
Authors: Vammen S , Lindholt J S , Østergaard L , Fasting H , Henneberg E W 
Published: March 2003

Abstract

Background
Macrolide treatment has been reported to lower the risk of recurrent ischaemic heart disease. The influence of macrolides on the expansion rate of abdominal aortic aneurysms (AAAs) remains unknown. The aim was to investigate the effect of roxithromycin on the expansion rate of small AAAs.

Methods
A total of 92 subjects with a small AAA were recruited from two populations. One population consisted of 6339 men aged 65–73 years who were offered a hospital-based mass screening programme for AAA. From this population 66 subjects were recruited. The remaining 26 men were recruited from among 49 subjects diagnosed at interval screening for an initial aortic diameter between 25 and 29 mm. Subjects were randomized to receive either oral roxithromycin 300 mg once daily for 28 days or matching placebo, and followed for a mean of 1·5 years.

Results
The mean annual expansion rate of AAAs was reduced by 43 per cent in the intervention group (1·56 mm per year), compared with 2·75 mm per year following placebo (P = 0·02). Multiple linear regression analysis showed that roxithromycin treatment and initial AAA size were significantly related to AAA expansion when adjusted for smoking, diastolic blood pressure and immunoglobulin A level of 20 enzyme immunounits or more. Logistic regression analysis confirmed a significant difference in expansion rates above 2 mm annually between the intervention and placebo groups: odds ratio = 0·09 (95 per cent confidence interval 0·01–0·75).

Conclusion
In comparison to placebo, roxithromycin 300 mg daily for 4 weeks reduced the expansion rate of AAAs.
Fate of the rectum in patients undergoing total colectomy for Crohn's disease
Authors: Cattan P , Bonhomme N , Panis Y , Lémann M , Coffin B , Bouhnik Y , Allez M , Sarfati E , Valleur P 
Published: March 2003

Abstract

Background
This study aimed to analyse disease recurrence and fate of the rectum in patients who had a total colectomy for Crohn's disease.

Methods
One hundred and forty-four patients who had a total colectomy for Crohn's colitis were reviewed retrospectively. Ileorectal anastomosis (IRA) was performed in 118 patients, while 26 never had an IRA after colectomy because of severe anorectal lesions. Factors associated with recurrence and rectal preservation failure were studied.

Results
The probability of clinical recurrence after IRA was 58 and 83 per cent at 5 and 10 years respectively. The probability of rectal preservation at 5 and 10 years was 70 and 63 per cent after colectomy, and 86 and 86 per cent after IRA, respectively. Patients with extraintestinal manifestation had a higher risk of recurrence and of rectal preservation failure. Previous ileal involvement was associated with a higher rate of ileal recurrence after IRA. After IRA, prophylactic treatment with 5-aminosalicylic acid was associated with a lower rate of recurrence and of failure to preserve the rectum.

Conclusion
Overall, 63 per cent of patients had a functioning IRA 10 years after total colectomy. Absence of extraintestinal manifestation and prophylactic treatment with 5-aminosalicylates after IRA were the main factors associated with long-term rectal preservation.
Identification of novel splice variants of the human catalytic subunit cβ of cAMP‐dependent protein kinase
Authors: Ørstavik Sigurd , Reinton Nils , Frengen Eirik , Langeland Bjørn Tore , Jahnsen Tore , Skålhegg Bjørn S. 
Published: March 2003

Four different isoforms of the catalytic subunit of cAMP‐dependent protein kinase, termed Cα, Cβ, Cγ and PrKX have been identified. Here we demonstrate that the human Cβ gene encodes six splice variants, designated Cβ1, Cβ2, Cβ3, Cβ4, Cβ4ab and Cβ4abc. The Cβ splice variants differ in their N‐terminal ends due to differential splicing of four different forms of exon 1 designated exon 1‐1, 1‐2, 1‐3, 1‐4 and three exons designated a, b and c. All these exons are located upstream of exon 2 in the Cβ gene. The previously identified human Cβ variant has been termed Cβ1, and is similar to the Cβ isoform identified in the mouse, ox, pig and several other mammals. Human Cβ2, which is the homologue of bovine Cβ2, has no homologue in the mouse. Human Cβ3 and Cβ4 are homologous to the murine Cβ3 and Cβ2 splice variants, whereas human Cβ4ab and Cβ4abc represent novel isofoms previously not identified in any other species. At the mRNA level, the Cβ splice variants reveal tissue specific expression. Cβ1 was most abundantly expressed in the brain, with low‐level expression in several other tissues. The Cβ3 and Cβ4 splice variants were uniquely expressed in human brain in contrast to Cβ2, which was most abundantly expressed in tissues of the immune system, with no detectable expression in brain.We suggest that the various Cβ splice variants when complexed with regulatory subunits may give rise to novel holoenzymes of protein kinase A that may be important for mediating specific effects of cAMP.
Tyrosine sulfation and N‐glycosylation of human heparin cofactor II from plasma and recombinant Chinese hamster ovary cells and their effects on heparin binding
Authors: Böhme Christoph , Nimtz Manfred , Grabenhorst Eckart , Conradt Harald S. , Strathmann Annemarie , Ragg Hermann 
Published: March 2003

The structure of post‐translational modifications of human heparin cofactor II isolated from human serum and from recombinant Chinese hamster ovary cells and their effects on heparin binding have been characterized. Oligosaccharide chains were found attached to all three potential N‐glycosylation sites in both protein preparations. The carbohydrate structures of heparin cofactor II circulating in blood are complex‐type diantennary and triantennary chains in a ratio of 6 : 1 with the galactose being > 90% sialylated with α2→6 linked N‐acetylneuraminic acid. About 50% of the triantennary structures contain one sLex motif. Proximal α1→6 fucosylation of oligosacharides from Chinese hamster ovary cell‐derived HCII was detected in > 90%	of the diantennary and triantennary glycans, the latter	being slightly less sialylated with exclusively α2→3‐linked N‐acetylneuraminic acid units. Applying the ESI‐MS/ MS‐MS technique, we demonstrate that the tryptic peptides comprising tyrosine residues in positions 60 and 73 were almost completely sulfated irrespective of the protein's origin. Treatment of transfected Chinese hamster ovary cells with chlorate or tunicamycin resulted in the production of heparin cofactor II molecules that eluted with higher ionic strength from heparin–Sepharose, indicating that tyrosine sulfation and N‐linked glycans may affect the inhibitor's interaction with glycosaminoglycans.
Agmatine oxidation by copper amine oxidase
Authors: Ascenzi Paolo , Fasano Mauro , Marino Maria , Venturini Giorgio , Federico Rodolfo 
Published: March 2003

The product of agmatine oxidation catalyzed by Pisum sativum L. copper amine oxidase has been identified by means of one‐ and two‐dimensional 1H‐NMR spectroscopy to be N‐amidino‐2‐hydroxypyrrolidine. This compound inhibits competitively rat nitric oxide synthase type I and type II (NOS‐I and NOS‐II, respectively) and bovine trypsin (trypsin) activity, values of Ki being (1.1 ± 0.1) × 10−5 m (at pH 7.5 and 37.0 °C), (2.1 ± 0.1) × 10−5 m (at pH 7.5 and 37.0 °C), and (8.9 ± 0.4) × 10−5 m (at pH 6.8 and 21.0 °C), respectively. Remarkably, the affinity of N‐amidino‐	2‐hydroxypyrrolidine for NOS‐I, NOS‐II and trypsin is significantly higher than that observed for agmatine and clonidine binding. Furthermore, N‐amidino‐2‐hydroxypyrrolidine and agmatine are more efficient than clonidine in displacing [3H]clonidine (= 1.0 × 10−8 m) from specific binding sites in heart rat membranes, values of IC50 being (1.3 ± 0.4) × 10−9 m and (2.2 ± 0.4) × 10−8 m, respectively (at pH 7.4 and 37.0 °C).
Mucosal tolerance as therapy of type I allergy: intranasal application of recombinant Bet v 1, the major birch pollen allergen, leads to the suppression of allergic immune responses and airway inflammation in sensitized mice
Authors: Winkler B. , Baier K. , Wagner S. , Repa A. , Eichler H.‐G. , Scheiner O. , Kraft D. , Wiedermann U. 
Published: March 2003

Background Several studies have demonstrated that mucosal administration of soluble antigens can prevent the onset or reduce the severity of certain autoimmune diseases or allergies. Few studies exist showing the efficacy of mucosal tolerance for therapy of such diseases.Objective The aim of the present study was to modulate an allergic immune response by intranasal antigen administration in an already sensitized organism.Methods A murine model of allergic asthma to birch pollen (BP) and its major allergen Bet v 1 was utilized. Sensitized mice were intranasally treated with recombinant (r)Bet v 1 in different concentrations and at different intervals. On the day the mice were killed, blood and bronchoalveolar lavage fluids were taken and immediate type I skin tests were performed. T cell proliferation and cytokine production (interleukin (IL)‐5, interferon (IFN)‐γ) were measured in spleen and lung cell cultures.Results Mucosal treatment with rBet v 1 (3 × 50 µg in 4 day intervals) led to a reduction of type I skin reactions, suppressed immunoglobulin (Ig)G1/IgE antibody levels and markedly decreased IL‐5 and IFN‐γ production in vitro in spleen and lung cell cultures. Moreover, lung inflammation (i.e. eosinophilia and IL‐5 levels in bronchoalveolar lavage fluids) was significantly suppressed by the treatment.Conclusion Our results demonstrate that intranasal treatment with rBet v 1 reduced systemic allergic immune responses as well as airway inflammation in BP‐sensitized mice. We therefore suggest that mucosal tolerance induction with recombinant allergens could be a promising concept for the therapy of allergic diseases.
Reciprocal patterns of allergen‐induced GATA‐3 expression in peripheral blood mononuclear cells from atopics vs. non‐atopics
Authors: Macaubas C. , Lee P. T. , Smallacombe T. B. , Holt B. J. , Wee C. , Sly P. D. , Holt P. G. 
Published: March 2003

Background T helper (Th)2 cytokines are considered to play a central role in the induction and expression of allergic disease. However, the relative importance of individual cytokines is unclear, and overall disease pathogenesis appears to involve the coordinate activities of a range of Th2 cytokines acting in sequence or in parallel. The present study examines an alternative approach to the study of cytokine gene function in atopy, focusing instead upon T cell transcription factors (TFs) which play a role in the regulation of multiple cytokine genes.Objective To investigate the allergen‐induced expression of the TF GATA‐3 and c‐Maf in peripheral blood mononuclear cells (PBMCs) and in cytokine‐driven Th polarization.Methods PBMC from house dust mite (HDM)‐atopic and non‐atopics were stimulated in vitro with allergen or anti‐CD3/IL‐2. TF expression was analysed by semiquantitative RT‐PCR and major findings were validated by real‐time PCR. Cell separations were performed to analyse the contribution of CD45RO+ cells. CD4+ cord blood cells were Th1 or Th2 polarized in vitro by exogenous cytokines and TF expression analysed by Northern blot and real‐time PCR.Results We demonstrate for the first time that during differentiation of CD4+ CD45RA+ naïve human T cells towards Th2 commitment, and during allergen‐specific reactivation of peripheral CD4+ CD45RO+ Th2 memory cells in established atopics, expression of the Th2‐associated TF GATA‐3 is rapidly up‐regulated, whereas T cells from non‐atopics display equally rapid GATA‐3 down‐regulation under identical conditions of allergen stimulation.Conclusion These findings identify Th2‐associated TFs as key determinants of the atopic phenotype, suggesting their unique potential as therapeutic targets for disease control.
Spatial and temporal habitat use of kob antelopes (Kobus kob kob, Erxleben 1777) in the Comoé National Park, Ivory Coast as revealed by radio tracking
Authors: Fischer Frauke , Linsenmair K. Eduard 
Published: March 2003

AbstractSpatial and temporal habitat use of kob antelopes (Kobus kob kob) have been investigated in the Comoé National Park (Ivory Coast, West Africa) by use of radio telemetry. A total of 23 kob were equipped with radio collars and radio tracked for up to 15 months. Home ranges of males were smaller and those of females larger than expected from theoretical models. Adult males used smaller areas than adult females and did not show seasonal home range shifts. Daily distances travelled did not differ between sexes. Kob walked less during the night than by day and covered shorter distances in the wet season. Whereas an increase in home range overlap between females resulted in higher rates of association among individuals, association of adults of mixed sexes was not correlated with the degree of home range overlap. Territorial behaviour of males and predator avoidance by females are suggested to explain the sex‐specific differences in home range size of adults and the deviation from the predicted sizes. Predator avoidance is presumed as the main reason for the reduced walking distances at night as well as in the wet season. Reproductive behaviour and feeding ecology are assumed to determine the degree of association of conspecifics.
Takayasu's arteritis associated with various neurological disorders and uveitis
Authors: Bohgaki Miyuki , Mukai Masaya , Notoya Atsushi , Kohno Michifumi , Tashiro Jun 
Published: March 2003

Abstract Introduction: This report describes a 51‐year‐old woman who presented with aseptic meningitis, polyneuropathy and uveitis associated with Takayasu's arteritis (TA). Clinical picture: The patient presented with high‐grade fever, vertigo, deafness and photopsia. Although systemic vasculitis involving small arteries was suspected from her symptoms and signs, aortitis and aortic arch vessel vasculitis were found by computed tomography. We diagnosed her as having TA. Treatment: Oral prednisolone therapy was administered to the patient. Outcome: After treatment, the patient's symptoms and the thickening of her vessel walls reduced. Conclusions: Although these symptoms associated with TA have been reported only rarely, it is suspected that they are associated with the same immunological pathogenesis as arteritis.
Intra‐articular hyaluronan in osteoarthritis: The clinical perspective
Authors: March L. 
Published: March 2003

A review of the efficacy of intra‐articular hyaluronan products for patients with osteoarthritis (OA) of the knee will be presented. A full Cochrane systematic review of these products is pending (see Cochrane Library, Bellamy et al. Protocol).The majority of published studies show advantages for hyaluronan and hylans over placebo for symptom modification including reduction in walking pain and improvement in physical function. The proportion of patients benefiting 6 months after their course of injections varies between published studies from 58 to 91%. Some of this variability may be accounted for by differences in baseline severity of OA as open‐labeled post‐marketing surveys have found that both the proportion of patients responding and the duration of response decreases with increasing radiological grades of OA. Patients with Grade IV OA changes were uniformly excluded from the controlled trials. Local audits suggest that less than 50% of patients are getting significant improvement from baseline. The reported rate of reactions following the injection is also variable ranging from less than 2% to more than 20% per patient. Reactions appear to be more frequent in people having a second course of injections.Despite the variability in response, the consistent positive trend has led all major international published guidelines for OA management to recommend a trial of intra‐articular hyaluronan for patients whose knee OA is not responding to adequate analgesic therapy and maximal non‐pharmacological measures.Whether hyaluronan also has structure modifying properties remains to be seen. One small arthroscopic study, reviewing histology before and after the injection course, found significant changes in articular cartilage parameters compared with intra‐articular corticosteroids. Another recent study, presented in abstract form, found a significant difference in joint space narrowing on standardised X‐rays between OA knee patients who had had 3 courses of hyaluronan (each of 3 injections) over a 12 month period and patients receiving placebo saline injections.Intra‐articular hyaluronan appears to have a role in symptom relief for some patients with OA of the knee. Those with more advanced radiological damage are less likely to get a response but may still gain some benefit. Patients need to be made aware of possible local reactions which may be more frequent in the setting of coexistent crystal deposition. Preliminary work suggests that intra‐articular HA has potential for structure modification but further research is required.
Mechanisms of bone re‐modeling, resorption and repair: Therapeutic strategies for intervention
Authors: Dunstan C. R. 
Published: March 2003

The skeleton is a dynamic structure contributing vitally to the body’s needs for structural support and mineral homeostasis. Bones are able to develop to appropriate size and shape, be renewed every 7–10 years, respond to changes in mechanical stress, repair and reshape after fracture, and support calcium homeostasis. The processes of bone modeling, remodeling and repair require the concerted actions of osteoclasts and osteoblasts. The activity of these cells is normally tightly regulated at the local level to initiate and direct these processes so as to maintain shape, strength and architecture of the skeleton. Systemic and local stimuli provide an integrated signal to bone cells to determine the initiation rate and duration of remodeling activity.In disease, the regulation of bone resorption and formation can break down giving rise to systemic or local bone loss that can impair structural integrity and/or mineral homeostasis. Disease processes overwhelm local structural signals to induce excessive bone resorption, inhibit bone formation, or induce loss of bone architecture. Therapeutic strategies that restore or enhance normal local responsiveness to physiologic signals are those most likely to induce repair that is structurally sound. Thus understanding of the mechanisms of local regulation of osteoclast and osteoblast function is vital to the development of effective therapeutics.The recent discovery of the importance of RANK signaling, as modulated by RANK ligand and osteoprotegerin (OPG), in regulating bone resorption, serves as an example of convergence of multiple systemic signals to a single signaling pathway active in the local bone environment. Inhibition of RANK signaling through treatment with recombinant OPG provides potent inhibition of bone resorption in multiple pathologic indications.Discovery of similar pathways regulating the activity of osteoblasts at the local level could give rise to additional therapeutic modalities to improve bone structure. Different strategies may be required to thicken current bone elements, rebuild trabecular structure, bridge large defects, and then to maintain these improvements.
The genetics of osteoporosis and the search for osteoporosis genes
Authors: Sambrook P. 
Published: March 2003

Osteoporosis represents a major or developing public health problem in most countries around the world. Because fracture, the clinical manifestation of the disease, is a time dependent event, bone mineral density (BMD) is most frequently used as a surrogate phenotype. Each standard deviation decrease in BMD is associated with an approximate twofold increase in fracture risk, which is similar to the magnitude of association between hypertension and cardiovascular disease. Thus, identifying factors that are involved in the determination of BMD is important in osteoporosis research.One of the remarkable features of BMD is that it is normally distributed with a virtually constant variance throughout life. Although BMD shows an age dependent pattern of an initial increase with growth and subsequent decline in later life, twin and family studies have shown that at each stage of life, genetic factors account for up to 70 to 80% of the variance of BMD. However multiple genes appear responsible for determining BMD at various skeletal sites.Two strategies have been used for identifying genes influencing BMD, namely genome‐wide scanning (a top down approach) and candidate genes (a bottom up approach). The latter has been most frequently used to date and two candidate genes have received the most attention, namely the vitamin D receptor and collagen genes. In 1994, a strong association between non‐coding polymorphisms in the vitamin D receptor gene and BMD was reported, although when genotyping errors were later accounted for, the effect was considerably weaker in magnitude. Numerous subsequent studies have reported an association between BMD and VDR genotypes ranging from a similar effect to no effect. In 1997, an association between polymorphisms in the collagen 1a1 gene and BMD was also reported. Again subsequent reports have supported the original findings but also shown no effect in some populations. Other candidate genes reported include the estrogen receptor, apolipoprotein E, TGFβ and IL‐6, all with varying strength of association and controversy. These discrepancies may be due to a variety of problems including inadequate study sample size, selection bias in the populations studies, gene environment effects, linkage dysequilibrium and genotyping errors. Determining the effects of gene–environment interactions on measured phenotypes is particularly complicated if multiple genetic loci are involved, as is likely, and the dose of ‘environmental exposure’ varies, as seems common between populations.For these reasons it is likely that the top down approach, of genome‐wide scanning in appropriate large scale twin or affected sib pair populations, will prove most effective in identifying clinically meaningful osteoporosis genes in the future.