tbuckley/cabot-search huggingface dataset:
Topical Granulocyte-Macrophage Colony- Stimulating Factor in Patients With Cancer and Impaired Wound Healing
Authors: M. Raderer, G. Kornek, M. Hejna, K. Koperna, W. Scheithauer, W. Base
Journal: JNCI Journal of the National Cancer Institute (1997)

Impaired wound healing in postsurgical patients and development of decubital ulcers in cachectic and immobilized patients is a commonly encountered problem. Those lesions cannot only prolong hospitalization but also render the affected patients more prone to infections and last, but not least, adversely influence quality of life. In view of the fact that recombinant granulocyte‐ macrophage colony-stimulating factor (GM‐CSF) has been reported to influence various epidermal cells and enhance wound healing (1,2), and because of promising results in patients with lepra ( 3), leg ulcers (4), and indolent wounds of various causes (5), we have treated 10 cancer patients with topical GM‐CSF. All patients had an underlying cancer and presented with nonhealing abdominal wounds after surgical intervention (two patients) or decubital ulcers (eight patients). All lesions had been refractory to various forms of treatment for at least 4 weeks to a maximum time span of 2.5 months, with a diameter ranging from 2 to 10 cm. In our pilot series, GM‐CSF was administered topically. A 400-mg vial of commercially
Identification and Characterization of Genetic Variation in the Folylpolyglutamate Synthase Gene
Authors: Tarek A. Leil, Chiaki Endo, Araba A. Adjei, Grace K. Dy, Oreste E. Salavaggione, Joel R. Reid, Matthew M. Ames, Alex A. Adjei
Journal: Cancer Research (2007)

Abstract Folylpolyglutamate synthase (FPGS) catalyzes the polyglutamation of folic acid, methotrexate, and pemetrexed to produce highly active metabolites. To characterize genetic variation in the FPGS gene, FPGS, have resequenced the gene in four different ethnic populations. Thirty-four single nucleotide polymorphisms were identified including five nonsynonymous coding single nucleotide polymorphisms that altered the FPGS protein sequence: F13L and V22I polymorphisms in the mitochondrial isoform of FPGS, and R466/424C, A489/447V, and S499/457F polymorphisms, which exist in both the mitochondrial and cytosolic isoforms. When expressed in AuxB1 cells, the A447V cytosolic variant was functionally similar to the wild-type cytosolic (WT Cyt) allozyme, whereas the R424C and S457F cytosolic variants were reduced by ∼2-fold in protein expression compared with WT Cyt (P &amp;lt; 0.01). The intrinsic clearance of glutamate was reduced by 12.3-fold (R424C, P &amp;lt; 0.01) and 6.2-fold (S457F, P &amp;lt; 0.01), whereas the intrinsic clearance of methotrexate was reduced by 4.2-fold (R424C, P &amp;lt; 0.05) and 5.4-fold (S457F, P &amp;lt; 0.05) in these two cytosolic variants when compared with the WT Cyt isoform. Additionally, the in vitro enzyme velocity at saturating pemetrexed concentrations was reduced by 1.6-fold (R424C, P &amp;lt; 0.05) and 2.6-fold (S457F, P &amp;lt; 0.01) compared with WT Cyt. AuxB1 cells harboring these same cytosolic variant allozymes displayed significant increases in the EC50 for folic acid and in the IC50 values for both methotrexate and pemetrexed relative to the WT Cyt form of FPGS. These observations suggest that genetic variations in FPGS may alter the efficacy of antifolate therapy in cancer patients. [Cancer Res 2007;67(18):8772–82]
Down-regulation of ERK but not MEK phosphorylation in cultured endothelial cells by repeated changes in cyclic stretch
Authors: Feng Shi, Yi-Jen Chiu, Youngsun Cho, Tara A. Bullard, Masahiro Sokabe, Keigi Fujiwara
Journal: Cardiovascular Research (2006)

Effects of cyclic stretch on endothelial cells are studied usually by exposing cells cultured under stretch-free conditions to some levels of cyclic stretch, but in vivo these cells experience both increase and decrease in stretch. Experiments were designed to study how endothelial cells maintained under certain levels of cyclic stretch responded to shifts in stretch frequencies and amplitudes.Confluent endothelial cells cultured on flexible silicone membranes with or without pre-stretching for 2-12 h were exposed to various levels of stretch amplitude or frequency and assayed for extracellular signal-regulated kinase 1/2 (ERK) phosphorylation.When endothelial cells without pre-stretching were cyclically stretched, ERK phosphorylation increased, peaking approximately 15 min and slowly decreased. In contrast, when pre-stretched cells were exposed to either higher or lower stretch condition, ERK phosphorylation transiently decreased within 5 min, indicating that some mechanism which down-regulated ERK phosphorylation was activated. Because phosphorylation of ERK kinase (MEK) was not inhibited in these cells, this mechanism targeted ERK directly, not the upstream kinases of the Ras-Raf-MEK-ERK cascade. Furthermore, this ERK down-regulation in pre-stretched cells was not induced by agonists, was inhibited by Na(3)VO(4) but not okadaic acid, and was detected in the cytosolic fraction. Repeated shifts in stretch conditions induced continuous down-regulation of ERK but not MEK phosphorylation.Endothelial cells are capable of down-regulating ERK phosphorylation in a cyclic stretch- and tyrosine phosphatase-dependent manner. Frequent changes in stretch conditions constitutively activated this ability, which could play some role in regulating ERK activity in endothelial cells in vivo.
Effectiveness of a meditation-based stress reduction program in the treatment of anxiety disorders
Authors: J Kabat-Zinn, A O Massion, J Kristeller, L G Peterson, K E Fletcher, L Pbert, W R Lenderking, S F Santorelli
Journal: American Journal of Psychiatry (1992)

This study was designed to determine the effectiveness of a group stress reduction program based on mindfulness meditation for patients with anxiety disorders.The 22 study participants were screened with a structured clinical interview and found to meet the DSM-III-R criteria for generalized anxiety disorder or panic disorder with or without agoraphobia. Assessments, including self-ratings and therapists' ratings, were obtained weekly before and during the meditation-based stress reduction and relaxation program and monthly during the 3-month follow-up period.Repeated measures analyses of variance documented significant reductions in anxiety and depression scores after treatment for 20 of the subjects--changes that were maintained at follow-up. The number of subjects experiencing panic symptoms was also substantially reduced. A comparison of the study subjects with a group of nonstudy participants in the program who met the initial screening criteria for entry into the study showed that both groups achieved similar reductions in anxiety scores on the SCL-90-R and on the Medical Symptom Checklist, suggesting generalizability of the study findings.A group mindfulness meditation training program can effectively reduce symptoms of anxiety and panic and can help maintain these reductions in patients with generalized anxiety disorder, panic disorder, or panic disorder with agoraphobia.
General practice orthopaedic outpatient referrals in North Staffordshire.
Authors: A K Ross, W A Davis, G Horn, R Williams
Journal: BMJ (1983)

A study was made of 813 orthopaedic referrals by 134 general practitioners in North Staffordshire. The referral rates showed no relation to practice list size or the doctors' previous orthopaedic experience. The published waiting times did not accurately reflect clinic vacancies, and no effective priority rating of letters by consultants was shown. Less than 1% of patients had an appointment within four weeks. One quarter of the patients failed to attend and, of those who did, 27% received physiotherapy or a "simple" appliance, or both, while 16% received treatment already available from their general practitioner. Patients from high referring doctors showed the same pattern of distribution in body area affected and treatment outcome as those from low referring doctors, but had a significantly longer time to wait for their appointment. A survey of non-attenders showed that 56% of the patients failed to attend because the condition had resolved.
A class of human exons with predicted distant branch points revealed by analysis of AG dinucleotide exclusion zones
Authors: Clare Gooding, Francis Clark, Matthew C Wollerton, Sushma-Nagaraja Grellscheid, Harriet Groom, Christopher WJ Smith
Journal: Genome biology (2006)

Abstract Background The three consensus elements at the 3' end of human introns - the branch point sequence, the polypyrimidine tract, and the 3' splice site AG dinucleotide - are usually closely spaced within the final 40 nucleotides of the intron. However, the branch point sequence and polypyrimidine tract of a few known alternatively spliced exons lie up to 400 nucleotides upstream of the 3' splice site. The extended regions between the distant branch points (dBPs) and their 3' splice site are marked by the absence of other AG dinucleotides. In many cases alternative splicing regulatory elements are located within this region. Results We have applied a simple algorithm, based on AG dinucleotide exclusion zones (AGEZ), to a large data set of verified human exons. We found a substantial number of exons with large AGEZs, which represent candidate dBP exons. We verified the importance of the predicted dBPs for splicing of some of these exons. This group of exons exhibits a higher than average prevalence of observed alternative splicing, and many of the exons are in genes with some human disease association. Conclusion The group of identified probable dBP exons are interesting first because they are likely to be alternatively spliced. Second, they are expected to be vulnerable to mutations within the entire extended AGEZ. Disruption of splicing of such exons, for example by mutations that lead to insertion of a new AG dinucleotide between the dBP and 3' splice site, could be readily understood even though the causative mutation might be remote from the conventional locations of splice site sequences.
Macrolides for the long-term management of asthma - a meta-analysis of randomized clinical trials
Authors: J. Reiter, N. Demirel, A. Mendy, J. Gasana, E. R. Vieira, A. A. Colin, A. Quizon, E. Forno
Journal: Allergy (2013)

Background Macrolide antibiotics, which have anti-inflammatory and immune modulatory effects, have been studied as adjuncts for the management of asthma. However, results have been contradictory and trials underpowered. We therefore sought to conduct a meta-analysis of randomized controlled trials (RCT). Methods All RCT of prolonged macrolides (3+ weeks) for asthma treatment, published up to January 2013 in MEDLINE, Scopus, CINAHL, Highwire, and The Cochrane Collaboration Library, were included. Fixed- or random-effects models were used to calculate pooled weighted or standard mean differences (WMD or SMD, respectively). Results A total of 12 studies were included for analysis. The pooled effect of macrolides on FEV1 (eight trials, 381 subjects) was not significant (SMD 0.05, 95% CI −0.14–0.25), but there was a significant increase in peak expiratory flow (four trials, 419 subjects; WMD 6.7, 95% CI 1.35–12.06). Pooled analysis also showed significant improvements in symptom scores (eight studies, 478 subjects; WMD −0.46, 95% CI −0.60 to −0.32), quality of life (five trials, 346 subjects; WMD 0.18, 95% CI 0.001–0.37), and airway hyper-reactivity (two trials, 131 subjects; SMD 1.99, 95% CI 0.46–3.52). Post hoc evaluation showed limited statistical power to detect significant differences in FEV1. Conclusions Macrolide administration for asthma for three or more weeks was not associated with improvement in FEV1, but produced significant improvements in peak expiratory flow, symptoms, quality of life, and airway hyper-reactivity. Macrolides may therefore be beneficial as adjunct asthma therapy. Future trials, focusing on long-term safety and effectiveness, should use standardized outcomes and procedures.
Demonstration of IgA and secretory component in human hepatocytes.
Authors: S M Hsu, P L Hsu
Journal: Gut (1980)

By the immunoperoxidase technique, immunoglobulin A(IgA) was demonstrated in 50% of human hepatocytes. The positively stained cells showed a tendency towards periportal clustering. Very few plasma cells were identified in the liver. The intrahepatocyte IgA is most probably derived from serum and on its way to the bile ducts. Secretory component (SC) had the same distribution as that of IgA. The presence of SC in the hepatocytes reflects either the synthesis of SC or the transport of pre-assembled SC-IgA by liver cells. The significance of transfer of IgA from serum into bile is as yet unknown. However, the transhepatic passage of IgA may represent a reinforcement of local intestinal immunity, as part of the gut-originated IgA antibodies, which fail to go through the intestinal mucosa, may still gain access to the lumen of the gut.
TLR3-mediated induction of Ro/SSA and La/SSB mRNA expression in salivary gland epithelial cells
Authors: Nikolaos C Kyriakidis, Efstathia K Kapsogeorgou, Vasiliki C Gourzi, Menelaos N Manoussakis, Haralampos M Moutsopoulos, Athanasios G Tzioufas
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background-objectives</h3> In-situ over-expression of Ro/SSA (Ro52/TRIM21 and Ro60/TROVE2) and La/SSB mRNAs has been previously described in the salivary gland epithelial cells (SGEC) of Sjögren9s syndrome (SS) patients. Recently, Ro52/TRIM21 has been shown to possess a regulatory role in TLR3-mediated inflammatory autoimmune responses. Herein, the authors examined whether TLR3 stimulation is implicated in the regulation of Ro52/TRIM21, as well as of Ro60/TROVE2 and La/SSB mRNA expression by SGEC. <h3>Materials-methods</h3> SGEC-lines from SS patients (n=5) and non-SS controls (n=8), were treated with the TLR3-ligand analogue polyinosinic:cytidylic acid (polyI:C, 5 µg/ml) and the TLR4-ligand lipopolysaccharide (LPS, 1 µg/ml, control TLR-treatment) for various time-points. The expression of Ro52/TRIM21, Ro60/TROVE2 and La/SSB mRNAs was analysed by real-time PCR at 0, 6, 12, 24 and 48 h of treatment. The results were normalised by the expression of the HPRT1 gene and calculated by the ΔΔCT method using HeLa as calibrator. Statistically significantly different mRNA expression was evaluated by non-parametric Mann–Whitney analysis. <h3>Results</h3> The basal (constitutive) mRNA expression levels of Ro52/TRIM21, Ro60/TROVE2 and La/SSB molecules were similar between SGEC lines from SS patients and controls. La/SSB and Ro60/TROVE2 mRNA levels were significantly upregulated following treatment of SGECs with polyI:C for 48 h (mean fold induction±SE: 1.87±0.19 and 2.38±0.31, respectively; p=0.004 each). PolyI:C was found to be a strong inducer of Ro52/TRIM21 mRNA expression by SGECs at 6 h of treatment (mean fold induction of basal expression±SE: 14.13±4.8, p&lt;0.0001). The polyI:C induced Ro52/TRIM21 mRNA expression remained stable until 12 h of treatment, whereas a further increment was observed at 48 h of treatment (mean fold induction: 33.4±9.8 compared to basal levels). SGECs obtained from SS patients and controls were found to respond similarly to TLR3 signaling. LPS treatment was not found to affect either Ro/SSA (Ro52/TRIM21 or Ro60/TROVE2) or La/SSB mRNA expression. <h3>Conclusion</h3> Our findings suggest that TLR3 signaling is implicated in Ro/SSA, and particularly, in Ro52/TRIM21 mRNA expression by SGECs. Further investigation is needed to clarify the mechanisms involved in this regulation.
Non-invasive ventilation in chronic obstructive pulmonary disease
Authors: K S. Babu
Journal: BMJ (2003)

Papers p 185 

Chronic obstructive pulmonary disease is a leading cause of global morbidity and mortality, and about 15% of adults in industrialised countries have chronic obstructive pulmonary disease when defined by spirometry. Mild exacerbations are common, and the development of hospital at home services for acute exacerbations has improved the treatment options for managing mild exacerbations safely in the community. Severe exacerbations, however, remain the largest single cause of emergency admissions for respiratory disease (far higher than for asthma), with a mean hospital stay of around 10 days. According to hospital episode statistics from the Department of Health, exacerbations of chronic obstructive pulmonary disease resulted in 135 000 admissions and just under a million bed days in England in 2000–1 (www.doh.gov.uk/hes). These account for over a third of the overall healthcare costs associated with treating chronic obstructive pulmonary disease in the United Kingdom. Exacerbations are not only expensive but can impair lung function and quality of life and are associated with further readmissions.

Severe exacerbations with impaired gas exchange are associated with death rates of up to 14%.1 In particular, admission to an intensive care unit and acute hypercapnic respiratory failure are associated with higher death rates—up to 59% at one year.2 …
Mountain biking injuries in rural England
Authors: L M Jeys, G Cribb, A D Toms, S M Hay
Journal: British Journal of Sports Medicine (2001)

Off road mountain biking is now an extremely popular recreation and a potent cause of serious injury.To establish the morbidity associated with this sport.Data were collected prospectively over one year on all patients presenting with an injury caused by either recreational or competitive off road mountain biking.Eighty four patients were identified, 70 males and 14 females, with a mean age of 22.5 years (range 8-71). Most accidents occurred during the summer months, most commonly in August. Each patient had an average of 1.6 injuries (n = 133) and these were divided into 15 categories, ranging from minor soft tissue to potentially life threatening. Operative intervention was indicated for 19 patients (23%) and several required multiple procedures. The commonest injuries were clavicle fractures (13%), shoulder injuries (12%), and distal radial fractures (11%). However, of a more sinister nature, one patient had a C2/3 dislocation requiring urgent stabilisation, one required a chest drain for a haemopneumothorax, and another required an emergency and life saving nephrectomy.This sport has recently experienced an explosion in popularity, and, as it carries a significant risk of potentially life threatening injury across all levels of participation, the use of protective equipment to reduce this significant morbidity may be advisable.
The Absolute Risk of Cervical Abnormalities in High-risk Human Papillomavirus–Positive, Cytologically Normal Women Over a 10-Year Period
Authors: Susanne Kjaer, Estrid Høgdall, Kirsten Frederiksen, Christian Munk, Adriaan van den Brule, Edith Svare, Chris Meijer, Attilla Lorincz, Thomas Iftner
Journal: Cancer Research (2006)

In spite of the success of cervical cytology as a cancer-screening tool, it has important limitations, and human papillomavirus (HPV) testing may be valuable in future screening. The majority of women in screened populations, who test HPV positive, will have a concurrent normal smear, and we need more information about the risk for subsequent high-grade cervical lesions in these women. We examined 8,656 younger women (22-32 years old) and 1,578 older women (40-50 years old) who were followed for development of cervical neoplasia (cytology and/or histology) through the Danish Pathology Data Bank. We estimated the proportion of women developing cervical lesions of different types before a given time point as a function of time. Among women with normal cytology and positive high-risk Hybrid Capture 2 (HC2) test, 17.7% and 24.5% of younger and older women, respectively, had a subsequent abnormal Pap smear within 5 years. The risk of CIN3 or cancer within 10 years among younger women with positive HC2 test was 13.6% (10.9-16.2) and 21.2% (2.7-36.1) among older women. An analysis among younger women also being HC2-positive 2 years before baseline showed a subsequent 10-year risk of > or =CIN3 of 18% (14.6-21.5). Among older women where HPV may be added to general screening, the estimated absolute risk of > or =CIN3 in HC2-positive women was more than 20% within 10 years. These results indicate that even a single positive HPV test in cytologically negative women is substantially predictive of high-grade CIN and suggest that HC2 testing can help stratify women into different risk categories.
Microgranular and t(11;17)/PLZF‐RARα variants of acute promyelocytic leukemia also present the flow cytometric pattern of CD13, CD34, and CD15 expression characteristic of PML‐RARα gene rearrangement
Authors: Edgar G. Rizzatti, Fernando L. Portieres, Sérgio L.R. Martins, Eduardo M. Rego, Marco A. Zago, Roberto P. Falcão
Journal: American Journal of Hematology (2004)

Acute promyelocytic leukemia (APL) is a subtype acute myeloid leukemia in which leukemic promyelocytes predominate in the bone marrow (BM). Rapid diagnosis is critical for treatment decision since all-trans-retinoic acid must be administrated promptly. The microgranular variant may be of difficult diagnosis, as it may be confused with other diseases on morphological grounds. The purpose of this study was to determine if the microgranular variant has the same antigenic profile as the classical hypergranular type. The immunophenotype of leukemic cells from the bone marrow of 50 patients, with the PML-RARalpha gene rearrangement confirmed by RT-PCR, was determined by flow cytometry using a large panel of 22 monoclonal antibodies and a polyclonal anti-TdT antibody. Thirty-four cases were classified as classical APL and 16 as microgranular APL. The immunophenotypic profile of the two subtypes was indistinguishable concerning the presence or absence of these antigens, including the absence of reactivity for the HLA-DR antigen. The simultaneous immunophenotypic combination of a unique major cell population, heterogeneous intensity of expression of CD13, and the typical pattern of CD15/CD34 expression were similarly present in the hypergranular and microgranular subtypes. Homogeneous expression of CD33 was observed in 76% of the classical APL cases and in 100% of the microgranular cases. Additionally, we have studied two cases of PLZF-RARalpha APL that also displayed the same immunophenotype described for classical APL. Thus, the immunophenotypic profile highly characteristic of the PML-RARalpha gene rearrangement was also observed in microgranular and PLZF-RARalpha variants of APL.
Clinical significance of upper airway dysfunction in motor neurone disease.
Authors: E Garcia-Pachon, J Marti, M Mayos, P Casan, J Sanchis
Journal: Thorax (1994)

To assess the occurrence, functional characteristics and prognostic value of upper airway dysfunction in motor neurone disease, 27 patients unselected for respiratory symptoms were studied.Upper airway function was evaluated by analysis of the maximal flow-volume loop. Neurological diagnosis was established from the clinical history and physical examination. The degree of impairment was quantified by the Appel score.Twelve patients (group A) showed abnormalities of the maximal flow-volume loop consistent with flow limitation (seven patients) or instability of upper airway function (gross oscillations of airflow, five patients). The remaining 15 patients (group B) exhibited a normal or generally reduced maximal flow-volume loop, suggestive of muscle weakness. No differences were observed between groups in general physical condition, rate of disease progression, or duration of disease.Upper airway dysfunction in patients with motor neurone disease was a frequent finding. It was present more often, but not exclusively, in patients with bulbar features and was unrelated to prognosis.