bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death
Authors: Chen Rong , Keating Michael J. , Gandhi Varsha , Plunkett William 
Published: June 2005

AbstractFlavopiridol is active against chronic lymphocytic leukemia (CLL) cells in vitro and in the treatment of advanced stage disease, but the mechanisms of these actions remain unclear. Originally developed as a general cyclin-dependent kinase inhibitor, flavopiridol is a potent transcriptional suppressor through the inhibition of positive transcription elongation factor b (P-TEFb; CDK9/cyclin T). P-TEFb phosphorylates the C-terminal domain (CTD) of RNA polymerase II to promote transcriptional elongation. Because most CLL cells are not actively cycling, and their viability is dependent upon the continuous expression of antiapoptotic proteins, we hypothesized that flavopiridol induces apoptosis in CLL cells through the transcriptional down-regulation of such proteins. This study demonstrated that flavopiridol inhibited the phosphorylation of the CTD of RNA polymerase II in primary CLL cells and reduced RNA synthesis. This was associated with a decline of the transcripts and the levels of short-lived antiapoptotic proteins such as myeloid cell leukemia 1 (Mcl-1), and resulted in the induction of apoptosis. The B-cell lymphoma 2 (Bcl-2) protein level remained stable, although its mRNA was consistently reduced, suggesting that the outcome of transcriptional inhibition by flavopiridol is governed by the intrinsic stability of the individual transcripts and proteins. The dependence of CLL-cell survival on short-lived oncoproteins may provide the biochemical basis for the therapeutic index in response to flavopiridol. (Blood. 2005;106:2513-2519)
MtDNA diversity among four Portuguese autochthonous dog breeds: a fine-scale characterisation
Authors: van Asch Barbara , Pereira Luísa , Pereira Filipe , Santa-Rita Pedro , Lima Manuela , Amorim António 
Published: June 2005

Abstract

Background
The picture of dog mtDNA diversity, as obtained from geographically wide samplings but from a small number of individuals per region or breed, has revealed weak geographic correlation and high degree of haplotype sharing between very distant breeds. We aimed at a more detailed picture through extensive sampling (n = 143) of four Portuguese autochthonous breeds – Castro Laboreiro Dog, Serra da Estrela Mountain Dog, Portuguese Sheepdog and Azores Cattle Dog-and comparatively reanalysing published worldwide data.

Results
Fifteen haplotypes belonging to four major haplogroups were found in these breeds, of which five are newly reported. The Castro Laboreiro Dog presented a 95% frequency of a new A haplotype, while all other breeds contained a diverse pool of existing lineages. The Serra da Estrela Mountain Dog, the most heterogeneous of the four Portuguese breeds, shared haplotypes with the other mainland breeds, while Azores Cattle Dog shared no haplotypes with the other Portuguese breeds.
A review of mtDNA haplotypes in dogs across the world revealed that: (a) breeds tend to display haplotypes belonging to different haplogroups; (b) haplogroup A is present in all breeds, and even uncommon haplogroups are highly dispersed among breeds and continental areas; (c) haplotype sharing between breeds of the same region is lower than between breeds of different regions and (d) genetic distances between breeds do not correlate with geography.

Conclusion
MtDNA haplotype sharing occurred between Serra da Estrela Mountain dogs (with putative origin in the centre of Portugal) and two breeds in the north and south of the country-with the Castro Laboreiro Dog (which behaves, at the mtDNA level, as a sub-sample of the Serra da Estrela Mountain Dog) and the southern Portuguese Sheepdog. In contrast, the Azores Cattle Dog did not share any haplotypes with the other Portuguese breeds, but with dogs sampled in Northern Europe. This suggested that the Azores Cattle Dog descended maternally from Northern European dogs rather than Portuguese mainland dogs. A review of published mtDNA haplotypes identified thirteen non-Portuguese breeds with sufficient data for comparison. Comparisons between these thirteen breeds, and the four Portuguese breeds, demonstrated widespread haplotype sharing, with the greatest diversity among Asian dogs, in accordance with the central role of Asia in canine domestication.
The morbidity and mortality following a diagnosis of peripheral arterial disease: Long-term follow-up of a large database
Authors: Caro Jaime , Migliaccio-Walle Kristen , Ishak Khajak J , Proskorovsky Irina 
Published: June 2005

Abstract

Background
Awareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need.

Methods
Morbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations.

Results
Half of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events.

Conclusion
A diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased.
Peripheral arterial disease: A high risk – but neglected – disease population
Authors: Tomson Joseph , Lip Gregory YH 
Published: June 2005

Abstract
Peripheral arterial disease (PAD) is a common, progressive manifestation of atherothrombotic vascular disease, which should be managed no different to cardiac disease. Indeed, there is growing evidence that PAD patients are a high risk group, although still relatively under-detected and under treated. This is despite the fact that PAD patients are an increased mortality rate comparable to those with pre-existing or established cardiovascular disease [myocardial infarction, stroke]. With a holistic approach to atherothrombotic vascular disease, our management of PAD can only get better.
Determinants of racial/ethnic differences in blood pressure management among hypertensive patients
Authors: Hicks LeRoi S , Shaykevich Shimon , Bates David W , Ayanian John Z 
Published: June 2005

Abstract

Background
Prior literature has shown that racial/ethnic minorities with hypertension may receive less aggressive treatment for their high blood pressure. However, to date there are few data available regarding the confounders of racial/ethnic disparities in the intensity of hypertension treatment.

Methods
We reviewed the medical records of 1,205 patients who had a minimum of two hypertension-related outpatient visits to 12 general internal medicine clinics during 7/1/01-6/30/02. Using logistic regression, we determined the odds of having therapy intensified by patient race/ethnicity after adjustment for clinical characteristics.

Results
Blacks (81.9%) and Whites (80.3%) were more likely than Latinos (71.5%) to have therapy intensified (P = 0.03). After adjustment for racial differences in the number of outpatient visits and presence of diabetes, there were no racial differences in rates of intensification.

Conclusion
We found that racial/ethnic differences in therapy intensification were largely accounted for by differences in frequency of clinic visits and in the prevalence of diabetes. Given the higher rates of diabetes and hypertension related mortality among Hispanics in the U.S., future interventions to reduce disparities in cardiovascular outcomes should increase physician awareness of the need to intensify drug therapy more agressively in patients without waiting for multiple clinic visits, and should remind providers to treat hypertension more aggressively among diabetic patients.
The combination of intravitreal triamcinolone and phacoemulsification surgery in patients with diabeticfoveal oedema and cataract
Authors: Habib Maged S , Cannon Paul S , Steel David HW 
Published: June 2005

Abstract

Background
The management of diabetic patients with refractory macular oedema or patients with no adequate pre-operative view to administer laser treatment provide a challenge to the ophthalmologist. We wished to assess the use, safety and effect of intravitreal triamcinolone injection at the time of cataract surgery in patients with diabetic foveal oedema and sight limiting lens opacities.

Method
This was a longitudinal non-randomised prospective pilot study in 18 eyes (12 patients). All patients had visually significant lens opacities and either persistent diabetic foveal oedema unresponsive to laser treatment-group A, or foveal oedema with no adequate pre-operative view for laser treatment- group B. The cataract surgery was carried out under full aseptic technique using a self-sealing temporal incision and a foldable acrylic lens. Intravitreal triamcinolone was given infratemporally pars plana at the completion of the cataract surgery. The patients were reviewed at day 5, 2 weeks, 2 months and then every 3 months as required. The Wilcoxin matched-pairs test was used to assess the significance of the improvement in visual acuity at 2 months.

Results
Twelve patients with a total of 18 eyes were included in the study. There were 10 patients (15 eyes) in group A and 3 patients (3 eyes) in group B. Preoperatively 16 of the 18 eyes had a visual acuity of 6/24 or worse. Postoperatively 83% of patients had completely dry foveae at 2 weeks. Best-corrected visual acuities at two months review ranged from 6/6 to CF with 9 eyes (50%) achieving 6/12 or better (7 eyes (47%) in group A and 2 eyes (67%) in group B). Three eyes had no recorded improvement in visual acuity, but no eyes had deterioration in acuity. The improvement in visual acuity was significant at p = 0.001. There were no significant sight threatening complications.

Conclusion
Intravitreal triamcinolone has been shown to lead to an improvement in macular oedema and visual improvement in diabetic patients not undergoing cataract surgery but has not, to our knowledge, been previously used in a study like this one.
We suggest that intravitreal injection at the time of cataract surgery could be carried out safely with encouraging visual outcomes in patients with diabetic foveal oedema and cataract.
Well-being in residency training: a survey examining resident physician satisfaction both within and outside of residency training and mental health in Alberta
Authors: Cohen Jordan S , Patten Scott 
Published: June 2005

Abstract

Background
Despite the critical importance of well-being during residency training, only a few Canadian studies have examined stress in residency and none have examined well-being resources. No recent studies have reported any significant concerns with respect to perceived stress levels in residency. We investigated the level of perceived stress, mental health and understanding and need for well-being resources among resident physicians in training programs in Alberta, Canada.

Methods
A mail questionnaire was distributed to the entire resident membership of PARA during 2003 academic year. PARA represents each of the two medical schools in the province of Alberta.

Results
In total 415 (51 %) residents participated in the study. Thirty-four percent of residents who responded to the survey reported their life as being stressful. Females reported stress more frequently than males (40% vs. 27%, p < 0.02). Time pressure was reported as the number one factor contributing to stress (44% of males and 57% of females). A considerable proportion of residents would change their specialty program (14%) and even more would not pursue medicine (22%) if given the opportunity to relive their career. Up to 55% of residents reported experiencing intimidation and harassment. Intimidation and harassment was strongly related to gender (12% of males and 38% of females). Many residents (17%) rated their mental health as fair or poor. This was more than double the amount reported in the Canadian Community Health Survey from the province (8%) or the country (7%).
Residents highly valued their colleagues (67%), program directors (60%) and external psychiatrist/psychologist (49%) as well-being resources. Over one third of residents wished to have a career counselor (39%) and financial counselor (38%).

Conclusion
Many Albertan residents experience significant stressors and emotional and mental health problems. Some of which differ among genders. This study can serve as a basis for future resource application, research and advocacy for overall improvements to well-being during residency training.
Secondary prevention of allergic symptoms in a dairy farmer by use of a milking robot
Authors: Korinth Gintautas , Broding Horst Christoph , Uter Wolfgang , Drexler Hans 
Published: June 2005

Abstract
Background
Animal-derived allergens include lipocalins which play an increasing role in occupational respiratory sensitizations. The prevention of sensitization in stock farming is often difficult due to intense exposure, with traditional milking still requiring close animal contact. Complete avoidance of allergen exposure is only possible if stock farming is abandoned. This is, however, often not feasible in small dairy plants because of the resulting loss of income.

Case presentation
In a 37-year-old female farmer daily asthmatic complaints appeared, associated with cow dust-derived allergen exposure by milking with a conventional device. Respiratory symptoms increased during a period of 12 years. Allergic bronchial asthma was diagnosed, caused by sensitization against cow dust-derived allergens, as demonstrated by positive skin prick test and by detection of IgE antibodies. In a separate specific inhalation challenge test using a 10% extract of cow dust-derived allergens a 330% increase of airway resistance was detected. To enable further dairy farming, a milking robot was installed in 1999, i.e., an automatic milking system. The novel milking technique reduced the daily exposure from over 2 hours to approximately 10 min. The clinical course after the installation of the milking robot was favourable, with less frequent allergic and asthmatic symptoms. Furthermore, asthma medication could be reduced. Improvement was noted also in terms of lung-function and decreased total serum IgE.

Conclusion
The case presented and the evidence from the literature indicates that the strategy of exposure minimization to allergens at workplaces can be an effective alternative to total elimination. In farmers with cow dust allergy a milking robot is an appropriate technical measure to minimize allergen-exposure.
Expression and functional properties of antibodies to tissue inhibitors of metalloproteinases (TIMPs) in rheumatoid arthritis
Authors: Bokarewa Maria , Dahlberg Leif , Tarkowski Andrej 
Published: June 2005

AbstractTissue inhibitors of matrix metalloproteinases (TIMPs) regulate the breakdown of extracellular matrix components and play an important role in tissue remodelling and growth, in both physiological and pathological conditions. We studied the autoimmune response to TIMPs in patients with rheumatoid arthritis (RA). Eighty-nine paired blood and synovial fluid samples from patients with RA were assessed for their reactivity with recombinant tissue inhibitors of metalloproteinases (TIMPs) 1 to 4 by an ELISA and were compared with blood from 62 healthy controls and 21 synovial fluid samples from patients with degenerative joint diseases. Presence of antibodies was established as the absorbance of the sample more than 2 standard deviations above the mean of the controls. In addition, immunoglobulin G (IgG) from blood samples of RA patients possessing TIMP antibodies was isolated on protein A–sepharose and tested for the in vitro ability to neutralize TIMP-2-dependent effects on metalloproteinase 9 (MMP9). Anti-TIMP antibodies were found in 56% of RA samples but in only 5% of the controls (P < 0.005). RA patients had high frequencies of antibodies against all TIMPs except TIMP-3. TIMP-2 antibodies were most frequently found (33%), being significantly more prevalent (P = 0.024) in patients with nonerosive than erosive RA. TIMP-1 antibodies were significantly more often found in synovial fluid samples than in the matched blood samples (P < 0.025). Importantly, the IgG fraction containing TIMP antibodies down-regulated the TIMP-2 inhibitory effect, thereby supporting MMP9 activity in vitro. In the present study, we show that RA patients frequently develop autoimmune response to TIMPs that may act as a functionally significant regulator of MMP activity and thereby of joint destruction.
Differential expression of chemokine receptors on peripheral blood B cells from patients with rheumatoid arthritis and systemic lupus erythematosus
Authors: Henneken Maren , Dörner Thomas , Burmester Gerd-Rüdiger , Berek Claudia 
Published: June 2005

AbstractChemokines and their receptors are essential in the recruitment and positioning of lymphocytes. To address the question of B cell migration into the inflamed synovial tissue of patients with rheumatoid arthritis (RA), peripheral blood naive B cells, memory B cells and plasma cells were analyzed for cell surface expression of the chemokine receptors CXCR3, CXCR4, CXCR5, CCR5, CCR6, CCR7 and CCR9. For comparison, B cells in the peripheral blood of patients with the autoimmune disease systemic lupus erythematosus (SLE) or with the degenerative disease osteoarthritis (OA) were analyzed. Expression levels of chemokine receptors were measured by flow cytometry and were compared between the different patient groups and healthy individuals. The analysis of chemokine receptor expression showed that the majority of peripheral blood B cells is positive for CXCR3, CXCR4, CXCR5, CCR6 and CCR7. Whereas a small fraction of B cells were positive for CCR5, practically no expression of CCR9 was found. In comparison with healthy individuals, in patients with RA a significant fraction of B cells showed a decreased expression of CXCR5 and CCR6 and increased levels of CXCR3. The downregulation of CXCR5 correlated with an upregulation of CXCR3. In patients with SLE, significant changes in CXCR5 expression were seen. The functionality of the chemokine receptors CXCR3 and CXCR4 was demonstrated by transmigration assays with the chemokines CXCL10 and CXCL12, respectively. Our results suggest that chronic inflammation leads to modulation of chemokine receptor expression on peripheral blood B cells. However, differences between patients with RA and patients with SLE point toward a disease-specific regulation of receptor expression. These differences may influence the migrational behavior of B cells.
Creation and disruption of protein features by alternative splicing - a novel mechanism to modulate function
Authors: Hiller Michael , Huse Klaus , Platzer Matthias , Backofen Rolf 
Published: June 2005

Abstract
Background
Alternative splicing often occurs in the coding sequence and alters protein structure and function. It is mainly carried out in two ways: by skipping exons that encode a certain protein feature and by introducing a frameshift that changes the downstream protein sequence. These mechanisms are widespread and well investigated.

Results
Here, we propose an additional mechanism of alternative splicing to modulate protein function. This mechanism creates a protein feature by putting together two non-consecutive exons or destroys a feature by inserting an exon in its body. In contrast to other mechanisms, the individual parts of the feature are present in both splice variants but the feature is only functional in the splice form where both parts are merged. We provide evidence for this mechanism by performing a genome-wide search with four protein features: transmembrane helices, phosphorylation and glycosylation sites, and Pfam domains.

Conclusion
We describe a novel type of event that creates or removes a protein feature by alternative splicing. Current data suggest that these events are rare. Besides the four features investigated here, this mechanism is conceivable for many other protein features, especially for small linear protein motifs. It is important for the characterization of functional differences of two splice forms and should be considered in genome-wide annotation efforts. Furthermore, it offers a novel strategy for ab initio prediction of alternative splice events.
Scintigraphic evaluation of nasal mucociliary activity in unilateral chronic otitis media
Authors: Cingi Cemal , Altin Fazilet , Cakli Hamdi , Entok Ernre , Gurbuz Kezban , Cingi Emre 
Published: June 2005

Mucociliary clearance is a key defence mechanism in human upper and lower airways. Although mucociliary activity is present in both ears of the patients, most cases of chronic otitis media are unilateral.In this study, we aim to evaluate the difference between nasal mucociliary activity of the affected and non-affected sides in patients with unilateral chronic otitis media. Both nasal transport times of 36 patients with unilateral chronic otitis media were compared statistically with each other and with the control group by independent samples t-test. The nasal mucociliary transport times of the nasal cavity at the same side as the affected ear and as the non-affected ear are significantly different, in the same patients.Our study shows that impaired or decreased nasal mucociliary activity may result in dysfunction of the eustachian tube and middle-ear ciliary activity, which plays an important role in the aetiopathogenesis of chronic otitis media.
Co-morbidity of migraine and Ménière’s disease – is allergy the link?
Authors: Sen Purushotham , Georgalas Christos , Papesch Michael 
Published: June 2005

This study determined the prevalence of migraine and allergy in patients with Ménière’s disease (MD) compared with age- and sex-matched controls. We tested the hypothesis that if migraine and MD is linked by allergy, then allergy should be more prevalent in patients with MD and migraine compared with MD patients without migraine.A web-based questionnaire was used to recruit patients with MD (n = 108) while the control group consisted of patients attending the ENT clinic for other problems (n = 100).The prevalence of migraine and allergy was significantly higher in patients with MD compared with age- and sex-matched controls (p ≥ 0.005). In addition, the prevalence of allergy was significantly higher in patients who had both MD and migraine (30/42) than MD alone (26/66,p = 0.002). However, there was no link with any specific allergy types.This study suggests that migraine and MD may be linked by an immunological determinant.