tbuckley/cabot-search huggingface dataset:
Prediction of Retinopathy at 20 Years After Onset in Younger-Onset Type 1 Diabetes Using Mean Metabolic Memory-Free HbA1c Values: The importance of using HbA1c data of total, not partial, diabetes duration
Authors: Akira Hirose, Daisuke Furushima, Naohito Yamaguchi, Shigehiko Kitano, Yasuko Uchigata
Journal: Diabetes Care (2013)

Metabolic memory, in which past hyperglycemia could affect future retinopathy, is a potential issue in studying the relationship between glycemia and retinopathy. We examined retrospectively if mean "metabolic memory-free" glycosylated hemoglobin A1C (HbA1c) values covering total diabetes duration could predict retinopathy in younger-onset type 1 diabetes mellitus (T1DM).Inclusion criteria were T1DM onset before age 30 years, first visit to our center between 1988 and 1990 soon after onset, continuous HbA1c data for 20 years, and a 20-year follow-up retinopathy examination. Retinopathy predictive capabilities of HbA1c variables were examined.Of 15 subjects, 5 were retinopathy-positive and 10 were retinopathy-negative at the 20-year follow-up. Mean metabolic memory-free HbA1c values for the 20 years showed a substantial capacity to predict retinopathy at 20 years. The longer the period without HbA1c data following onset in simulation, the less accurate the prediction.HbA1c values may predict retinopathy better if metabolic memory-free data are used.
Oligonucleotides antisense to the interleukin 1 receptor mRNA block the effects of interleukin 1 in cultured murine and human fibroblasts and in mice.
Authors: R M Burch, L C Mahan
Journal: Journal of Clinical Investigation (1991)

Phosphodiester and phosphorothioate oligodeoxynucleotides (18 mers) were constructed antisense to sequences of the recently cloned murine and human IL-1 receptors. Murine antisense oligonucleotides inhibited IL-1-stimulated PGE2 synthesis by murine fibroblasts in culture in a time (days) and concentration-dependent (3 microM-30 microM) fashion. Murine sense oligonucleotide and an oligonucleotide antisense to human IL-1 receptor were without effect. Moreover, murine antisense oligonucleotides did not affect tumor necrosis factor- or bradykinin-stimulated PGE2 synthesis by murine fibroblasts. Similarly, antisense oligonucleotides to the human, but not the murine, IL-1 receptor inhibited IL-1-stimulated PGE2 synthesis by cultured human fibroblasts. The attenuation of the cellular response to IL-1 caused by the antisense oligonucleotides correlated with a loss in cell surface receptors for IL-1, without any change in the number of bradykinin receptors on these cells. When antisense oligonucleotides were encapsulated in liposomes, they blocked completely the appearance of newly synthesized IL-1 receptors and IL-1-stimulated PGE2 synthesis. In mice, subcutaneous injection with an oligonucleotide antisense to the murine IL-1 receptor markedly inhibited the infiltration of neutrophils in response to subsequent injection of IL-1. These data suggest that antisense oligodeoxynucleotides may share a role in the design of antiinflammatory therapeutics.
A<scp>sthma</scp>: Mechanisms of Disease Persistence and Progression
Authors: Lauren Cohn, Jack A. Elias, Geoffrey L. Chupp
Journal: Annual Review of Immunology (2004)

When asthma is diagnosed, eosinophilic inflammation and airway remodeling are established in the bronchial airways and can no longer be separated as cause and effect because both processes contribute to persistence and progression of disease, despite anti-inflammatory therapy. Th2 cells are continually active in the airways, even when disease is quiescent. IL-13 is the key effector cytokine in asthma and stimulates airway fibrosis through the action of matrix metalloproteinases on TGF-beta and promotes epithelial damage, mucus production, and eosinophilia. The production of IL-13 and other Th2 cytokines by non-T cells augments the inflammatory response. Inflammation is amplified by local responses of the epithelium, smooth muscle, and fibroblasts through the production of chemokines, cytokines, and proteases. Injured cells produce adenosine that enhances IL-13 production. We review human and animal data detailing the cellular and molecular interactions in established allergic asthma that promote persistent disease, amplify inflammation, and, in turn, cause disease progression.
Identification of a Potentially Radiosensitive Subgroup Among Patients With Breast Cancer
Authors: Martin F. Lavin, Ian Bennett, Jonathan Ramsay, Robert A. Gardiner, Greg J. Seymour, Aine Farrell, Michael Walsh
Journal: JNCI Journal of the National Cancer Institute (1994)

The description of genes and genetic syndromes, such as ataxia-telangiectasia, that predispose some women to breast cancer will provide greater insight into the genetic basis of cancer susceptibility. Our goal was to establish cell lines from patients with breast and bladder cancers, to screen for enhanced levels of radiation-induced arrest in the G 2 phase of the cell cycle such as is observed in ataxia-telangiectasia heterozygotes, and to correlate G 2 arrest with other prognostic indicators of these cancers and in vivo radiosensitivity. Epstein-Barr virus-transformed lymphoblastoid cells were established from 108 female patients with breast cancer and 24 age-matched female control subjects, and from 45 patients with bladder cancer and 18 age-matched control subjects. Cells were exposed to 3 Gy of γy radiation, and the percentages of cells in G 1 , and G 2 phases were determined at 18 and 24 hours after irradiation by fluores cence-activated cell sorter analysis. Postirradiation delay in G 2 phase was determined by calculating the percentage of cells in G 2 and by using the ratio G 2 /G 1 . When we determined the percentage of cells in G 2 phase at 18 hours after irradiation in 108 lym phoblastoid cells from breast cancer patients, we observed an increase of be-tween 3% and 38% in the number of cells in G 2 phase in comparison with cells that were not irradiated. Comparison with previous G 2 -phase arrest data for ataxia-telangiectasia hetero zygotes using a cutoff point at 29% delay demonstrated that 20% and 8% of the breast cancer cell lines of the case patients and control subjects, respectively, fell into that category ( P <.001). At the same time after irradiation, it was not possible to distinguish between bladder cancer cell lines (7%) and those of the corresponding control group (6%). Assessment of radiation effects by G 2 /G 1 ratio showed that 18 of the breast cancer patients and 8% of the control subjects were in the high range. When G 2 arrest was correlated with other prognostic factors, we found that case patients with a greater G 2 block were more likely to have had a family history of breast cancer ( P <.006) and more aggressive tumors when assessed by number of involved lymph nodes ( P )<.002) and tumor size ( P <.05). Furthermore, an adverse response to radiotherapy was observed in a group of patients with high G 2 arrest. While the postirradiation increase in G 2 -phase arrest in cells from breast cancer patients observed in this study may indicate genetic heterozygosity for ataxia-telangiectasia, it might also reflect other genetic abnormalities im portant to breast cancer. [J Natl Cancer Inst 86:1627-1634, 1994]
Notch Activation as a Driver of Osteogenic Sarcoma
Authors: Jianning Tao, Ming-Ming Jiang, Lichun Jiang, Jason S. Salvo, Huan-Chang Zeng, Brian Dawson, Terry K. Bertin, Pulivarthi H. Rao, Rui Chen, Lawrence A. Donehower, Francis Gannon, Brendan H. Lee
Journal: Cancer Cell (2014)
New kits on the blot—can we microarray the future of atherosclerosis?
Authors: J Herrmann
Journal: Cardiovascular Research (2003)

See article by Martinet et al. [19] in this issue .

Cardiovascular diseases (CVDs) have a long track record, reaching pandemic proportions with the industrialization of the world. Current estimates of the World Health Organization project that, in less than 7 years from now, CVD will become the leading cause of death in developing countries and that, in less than 13 years from now, 25 million people will die from CVD on a global scale each year [1]. A major proportion of these CVD deaths will be related to atherosclerotic CVD (ASCVD) and, particularly, to its complication stage [2]. Hence, there is a strong call to the cardiovascular research community to identify pivotal mediators of atherosclerotic lesion formation and complication which at some point may turn into therapeutic targets.

What may be considered as searching for a needle in a haystack has been tremendously facilitated by the availability of the microarray technique. This technique, which allows the detection of labeled RNA hybridizing to DNA molecules attached to a solid surface, evolved in a number of steps in the 1960s and 1970s and was finally moved to high capacity in the 1990s [3,4]. Microarray plates with a density of >250,000 oligonucleotides or >10,000 cDNA per cm2 currently serve as a versatile screening probe in genomics research, and it will not be long until arrays become available that allow the screening of the entire genome on one chip for less than one cell and 1 μg of tissue [5,6]. With regard to cardiovascular medicine, DNA microarray assays have already identified a three-digit number of genes potentially involved in atherosclerosis [7–16].

As marvelous as these assays are, they are not without concern. Indeed, a number of potential pitfalls to these kinds of genomic studies have been reported, … 

*Tel.: +1-507-255-1296; fax: +1-507-255-1824. Email address: herrmann.joerg{at}mayo.edu
Use of systematic reviews in clinical practice guidelines: case study of smoking cessation
Authors: C A Silagy, L F Stead, T Lancaster
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To examine the extent to which recommendations in the national guidelines for the cessation of smoking are based on evidence from systematic reviews of controlled trials. <b>Design:</b> Retrospective analysis of recommendations for the national guidelines for the cessation of smoking. <b>Materials:</b> National guidelines in clinical practice on smoking cessation published in English. <b>Main outcome measures:</b> The type of evidence (systematic review of controlled trials, individual trials, other studies, expert opinion) used to support each recommendation. We also assessed whether a Cochrane systematic review was available and could have been used in formulating the recommendation. <b>Results:</b> Four national smoking cessation guidelines (from Canada, New Zealand, the United Kingdom, and the United States) covering 105 recommendations were identified. An explicit evidence base for 100%, 89%, 68%, and 98% of recommendations, respectively, was detected, of which 60%, 56%, 59%, and 47% were based on systematic reviews of controlled studies. Cochrane systematic reviews could have been used to develop between 39% and 73% of recommendations but were actually used in 0% to 36% of recommendations. The UK guidelines had the highest proportion of recommendations based on Cochrane systematic reviews. <b>Conclusions:</b> Use of systematic reviews in guidelines is a measure of the "payback" on investment in research synthesis. Systematic reviews commonly underpinned recommendations in guidelines on smoking cessation. The extent to which they were used varied by country and there was evidence of duplication of effort in some areas. Greater international collaboration in developing and maintaining an evidence base of systematic reviews can improve the efficiency of use of research resources.
Smaller Nasal Volumes as Stigmata of Aberrant Neurodevelopment in Schizophrenia
Authors: Paul J Moberg, David R Roalf, Raquel E Gur, Bruce I Turetsky
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Anatomical and functional deficits of the olfactory neural system have been identified in patients with schizophrenia. Since olfactory structures develop in conjunction with both the palate and ventral forebrain, the authors hypothesized that schizophrenia patients might have structural abnormalities of the nasal cavity, which could represent specific markers of embryological dysmorphogenesis underlying schizophrenia. METHOD: A measurement of nasal volume was acquired by acoustic rhinometry for 40 male schizophrenia patients and 24 healthy male comparison subjects. RESULTS: The patients had smaller posterior nasal volumes than the comparison subjects but did not differ in anterior nasal volumes. This difference persisted after covarying for height and smoking history. CONCLUSIONS: The lower observed posterior nasal volume likely reflects a specific developmental craniofacial abnormality. This finding confirms an early disruption in embryological development in males with schizophrenia and may represent a genetic or environmental “first hit” that leaves the individual vulnerable to subsequent pathology.
The T-box transcription factor, TBX3, is sufficient to promote melanoma formation and invasion
Authors: Jade Peres, Sharon Prince
Journal: Molecular Cancer (2013)

The T-box transcription factor, TBX3, is overexpressed in several cancers and has been proposed as a chemotherapeutic target. Several lines of evidence suggest that TBX3 may be a key contributor to malignant melanoma, a highly aggressive and intractable disease. Using in vitro and in vivo assays we demonstrate here for the first time that overexpressing TBX3 in non-tumourigenic early stage melanoma cells is sufficient to promote tumour formation and invasion. Furthermore, we show that TBX3 may play an important role as a reciprocal switch between substrate dependent cell proliferation and tumour invasion.
Cerebral calcifications in an elderly lupus patient
Authors: V Filloux
Journal: Annals of the Rheumatic Diseases (2003)

reuil et al reported on a patient with Erdheim-Chester disease. 1 We would like to add our experience in a patient who had a good response to steroids.A 46 year old housewife, born in Maceio (Brazil), complained of pain in her legs for a period of eight months, which interfered with her sleep; there were no constitutional symptoms, such as weight loss, asthenia, or fever.On physical examination, there was no systemic involvement or bone inflammation, except for tenderness on palpation of both tibiae.An x ray examination showed bilateral and symmetrical cortical osteosclerosis of the diaphysial regions of the tibiae, which was better illustrated with magnetic resonance imaging (MRI) which showed a low signal on T 1 and a high signal on T 2 of the medullar canal (fig 1).Bone scintigraphy showed intense hypercapitation at the upper and medial regions of the right tibia and the medial region of the left tibia (fig 2).Other MR images (brain, thorax, and abdomen) were normal.A bone biopsy showed only osteosclerosis, which has been described in this disease. 2 She was treated with steroids for six months (prednisone 20 mg/day) and responded well, being asymptomatic and receiv-ing no treatment since December 2000.As bone pain is the first symptom of this xanthogranulomatosis, rheumatologists should be able to recognise the disease in an early phase when treatment gives a better outcome.. . . .
Lung function abnormalities and respiratory muscle weakness in children with juvenile chronic arthritis
Authors: L.M.e. Knook, I.m. de Kleer, C.K. van der Ent, J.j. van der Net, B.j. Prakken, W. Kuis
Journal: European Respiratory Journal (1999)

In contrast to adult rheumatoid arthritis (RA) little is known about the prevalence, nature and cause of lung function abnormalities in children with juvenile chronic arthritis (JCA). The aim of this study was to determine whether children with polyarticular and systemic onset JCA have lung function abnormalities and if so, whether they are related to pulmonary disease, thoracic and/or muscular involvement. We determined lung function and disability in 31 children with polyarticular and systemic JCA. Respiratory muscle function, thorax expansion and spine mobility were determined in the same patients, as well as in 32 matched healthy children. Peak expiratory flow (PEF) and forced vital capacity (FVC) were significantly reduced in JCA patients, when compared to reference values. Thorax expansion and spine mobility were normal, compared to paired controls. Maximum inspiratory (PI,max) and expiratory (PE,max) pressures were significantly reduced in patients compared to paired control subjects. A positive correlation was found between PE,max and FVC and PEF, an inverse correlation between expiratory pressure and disability. In conclusion, children with polyarticular and systemic juvenile chronic arthritis show a pronounced impairment in respiratory muscle strength, severe enough to cause mild lung function abnormalities and an increase in disability-scores.
Neurogenic electrical responses of single smooth muscle cells of the dog middle cerebral artery.
Authors: H Suzuki, S Fujiwara
Journal: Circulation Research (1982)

Electrical responses induced by perivasascular nerve stimulation were recorded intracellularly from the smooth muscle of dog middle cerebral artery. With nerve stimulation, the muscle membrane produced excitatory junction potential and then a slow hyperpolarization. The excitatory junction potential showed facilitation and the slow hyperpolarization showed depression phenomena, when the nerves were stimulated with twin pulses. Generation of the slow hyperpolarization was associated with an increase in the potassium conductance of the membrane and was suppressed by tetraethylammonium, which depolarized the membrane, reduced the membrane conductance, and increased the amplitude of the excitatory junction potential. Treatment with 6-hydroxydopamine abolished the excitatory junction potential, but not the slow hyperpolarization; the latter was suppressed by tetrodotoxin. The amplitude of slow hyperpolarization was decreased by application of tetraethylammonium or ATP, but was not affected by application of atropine, neostigmine, theophylline, apamin, ouabain, norepinephrine, propranolol, or guanethidine. ATP produced transient depolarization of the membrane with associated decrease in the membrane resistance. The excitatory junction potential was attributed to activation of the noradrenergic nerves, whereas the slow hyperpolarization was not generated by activation of adrenergic, cholinergic, or purinergic receptors. Inasmuch as the electrogenic Na-K pump, cAMP, and ATP were not involved in the generation of slow hyperpolarization, the possibility of an unidentified chemical transmitter should be given attention.
A global registry for idiopathic pulmonary fibrosis: the time is now
Authors: Christopher J. Ryerson, Tamera J. Corte, Harold R. Collard, Luca Richeldi
Journal: European Respiratory Journal (2014)

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease (ILD) of unknown aetiology with a median survival of only 3 years [1]. As a rare and orphan disease, IPF is difficult to study even within specialised referral centres and regional collaborative networks [2]. Although some local and regional prospective IPF registries exist, they generally do not share methodology and are not easily combined.

A global IPF registry would facilitate a better understanding of disease biology and behaviour [3], as well as identification of regional variations in diagnostic and management patterns that will help establish best practices [4]. Moreover, a global IPF registry would create a network for more efficient and affordable clinical trial conduct [5–7], and provide a platform for collaboration among stakeholders (patients, caregivers, clinicians, researchers, professional and scientific societies, industry partners, and governments).

We believe it is time to actively develop a global registry for IPF patients. The disease and the patients who suffer from it cannot wait. We propose a 5-year plan to achieve this goal (fig. 1).



Figure 1– 
Major steps and the timeline for the development of a global idiopathic pulmonary fibrosis (IPF) registry. It …
Relative impact of HLA phenotype and CD4-CD8 ratios on the clinical expression of hemochromatosis
Authors: G Porto, C Vicente, M A Teixeira, O Martins, J M Cabeda, R Lacerda, C Gonçalves, J Fraga, G Macedo, B M Silva, H Alves, B Justiça, M de Sousa
Journal: Hepatology (1997)

ABSTRACT Hemochromatosis is a hereditary iron–overload disease linked to HLA. The clinical expression of hemochromatosis is influenced by sex and age. However, other factors must account for the notorious heterogeneity of expression of the disease independent of sex, age, and HLA phenotype. The present study attempts to clarify some of these additional factors based on exhaustive statistical analysis of data collected from 43 selected patients with hemochromatosis. The statistical analysis focused on three groups of variables: the first group included variables reflecting the clinical expression of the disease; the second group represented the biochemical and hematological values at the time of diagnosis; and the third group consisted of the independent variables sex, age, HLA phenotype, and T–cell subset profile, i.e., the percentages and total numbers of CD4+ and CD8+ cells and the CD4–CD8 ratios. The results show that the relative expansion of the two main T–cell subsets, in the context of the HLA phenotype, correlates significantly with the clinical expression of hemochromatosis and the severity of iron overload. The present findings substantiate further the postulate that T cells have a role in the regulation of iron metabolism.
c-Met Is a Potentially New Therapeutic Target for Treatment of Human Melanoma
Authors: Neelu Puri, Salman Ahmed, Varalakshmi Janamanchi, Maria Tretiakova, Osvaldo Zumba, Thomas Krausz, Ramasamy Jagadeeswaran, Ravi Salgia
Journal: Clinical Cancer Research (2007)

Abstract Purpose: c-Met is a receptor tyrosine kinase involved in cell growth, invasion, metastases, and angiogenesis. In this study, we investigated the role of c-Met in melanoma biology using a novel small-molecule tyrosine kinase inhibitor SU11274 and small interfering (si) RNA against the receptor. Experimental Design: The effects of SU11274 and c-Met siRNA were studied on proliferation, apoptosis, differentiation, reactive oxygen species, and intracellular signaling. c-Met mutations were examined, and the expression of c-Met and activated c-Met was studied in nevi, primary, and metastatic melanoma. Results: c-Met was expressed in 6:7 melanoma cell lines by immunoblotting. SU11274 inhibited cell growth in all melanoma cell lines by 85% to 98% with an IC50 between 1 and 2.5 μmol/L and caused apoptosis (12-58%) in five out of six cell lines. siRNA against c-Met inhibited proliferation of melanoma cells by 60%. This is the first study that shows that SU11274 and siRNA induced microphthalmia-associated transcription factor (MITF) and several other melanoma differentiation proteins and a morphologically differentiated phenotype. SU11274 also inhibited reactive oxygen species formation and phosphorylation of c-Met receptor, AKT and S-6 kinase by the hepatocyte growth factor. A new missense c-Met mutation N948S was identified in cell lines and R988C in tumor tissue in the juxtamembrane domain of c-Met. It was found that c-Met was expressed in 88% of melanomas and 15% of nevi, and that c-Met (pY1003) was activated in 21% of human melanomas. Conclusion: These results support the role of c-Met in proliferation, apoptosis, differentiation, and tumor progression of melanoma. SU11274 could be used in the therapeutic inhibition of melanoma.
Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument
Authors: C Tropé, J Kaern, T Hogberg, V Abeler, B Hagen, G Kristensen, M Onsrud, E Pettersen, P Rosenberg, R Sandvei, K Sundfor, I Vergote
Journal: Annals of Oncology (2000)