tbuckley/cabot-search huggingface dataset:
Essential Role of Nuclear Factor (NF)-κB–Inducing Kinase and Inhibitor of κb (Iκb) Kinase α in Nf-κb Activation through Lymphotoxin β Receptor, but Not through Tumor Necrosis Factor Receptor I
Authors: Akemi Matsushima, Tsuneyasu Kaisho, Paul D. Rennert, Hiroyasu Nakano, Kyoko Kurosawa, Daisuke Uchida, Kiyoshi Takeda, Shizuo Akira, Mitsuru Matsumoto
Journal: The Journal of Experimental Medicine (2001)

Both nuclear factor (NF)-kappaB-inducing kinase (NIK) and inhibitor of kappaB (IkappaB) kinase (IKK) have been implicated as essential components for NF-kappaB activation in response to many external stimuli. However, the exact roles of NIK and IKKalpha in cytokine signaling still remain controversial. With the use of in vivo mouse models, rather than with enforced gene-expression systems, we have investigated the role of NIK and IKKalpha in signaling through the type I tumor necrosis factor (TNF) receptor (TNFR-I) and the lymphotoxin beta receptor (LTbetaR), a receptor essential for lymphoid organogenesis. TNF stimulation induced similar levels of phosphorylation and degradation of IkappaBalpha in embryonic fibroblasts from either wild-type or NIK-mutant mice. In contrast, LTbetaR stimulation induced NF-kappaB activation in wild-type mice, but the response was impaired in embryonic fibroblasts from NIK-mutant and IKKalpha-deficient mice. Consistent with the essential role of IKKalpha in LTbetaR signaling, we found that development of Peyer's patches was defective in IKKalpha-deficient mice. These results demonstrate that both NIK and IKKalpha are essential for the induction of NF-kappaB through LTbetaR, whereas the NIK-IKKalpha pathway is dispensable in TNFR-I signaling.
Assessment of gastrointestinal and cardiovascular risk in patients with osteoarthritis who require NSAIDs: the LOGICA study
Authors: A. Lanas, J. Tornero, J. L. Zamorano
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Medical management of adults with osteoarthritis (OA) who require non-steroidal anti-inflammatory drugs (NSAIDs) must be decided after assessing prevalent gastrointestinal (GI) and cardiovascular (CV) risks in the individual patient. <h3>Objective</h3> To evaluate the GI and CV risk profile of patients with OA who require NSAIDs. <h3>Methods</h3> A transversal, multicentre and observational study was conducted in consecutive patients with OA who were considered candidates for NSAID treatment and were visited by 374 unselected rheumatologists throughout the National Health System. Patients were classified into three risk groups (low, moderate and high) for their GI and CV characteristics. These were defined by considering the presence of a number of well-established GI risk factors or by application of the Systematic Coronary Risk Evaluation model for assessing the overall risk for CV disease, respectively. <h3>Results</h3> Of 3293 consecutive patients, most (86.6%) were at increased GI risk and a considerable number, 22.3%, were at high GI risk. The CV risk was high in 44.2% of patients, moderate in 28.5% and low in 27.3%. Overall, 15.5% of patients presented a very high-risk profile, having high GI and CV risks. The type of NSAID prescription was similar regardless of the associated GI and CV risk profile. <h3>Conclusion</h3> Most patients with OA requiring NSAIDs for pain control showed a high prevalence of GI and CV risk factors. Over half of the patients were at either high GI or CV risk, or both, such that the prescription of OA treatments should be very carefully considered.
Medial epicondylitis: is ultrasound guided autologous blood injection an effective treatment?
Authors: S P Suresh, K E Ali, H Jones, D A Connell
Journal: British Journal of Sports Medicine (2006)

Objective: To assess if ultrasound guided autologous blood injection is an effective treatment for medial epicondylitis. Methods: Twenty patients (13 men, 7 women) with refractory medial epicondylitis with symptom duration of 12 months underwent sonographic evaluation. Tendinosis was confirmed according to three sonographic criteria: echo texture, interstitial tears and neovascularity. The tendon was then dry needled and autologous blood was injected. Patients were reviewed at 4 weeks and at 10 months. VAS scores and modified Nirschl scores were assessed pre-procedure and post-procedure. Results: There was significant reduction in VAS pain score between pre-procedure and 10 months post-procedure when it had a median (IQR) of 1.00 (1–1.75), range 0–7. The median (IQR) Nirschl score, which at pre-procedure was 6.00 (5–7), range 4–7, had decreased at 4 weeks to 4.00 (2.25–5), range 2–7, and at 10 months to 1.00 (1–1.75), range 0–7, revealing a significant decrease (z = 3.763, p&lt;0.001). The hypo-echoic change in the flexor tendon significantly decreased between pre-procedure, when there was a mean (SD) of 6.45 (1.47), and at 10 months, when it was 3.85 (2.37) (p&lt;0.001). Doppler ultrasound showed that neovascularity decreased between pre-procedure, when there was a mean (SD) of 6.10 (1.62), range 4–9, and at 10 months, when it was 3.60 (2.56), range 0–9 (p&lt;0.001). Discussion: The combined action of dry needling and autologous blood injection under ultrasound guidance appears to be an effective treatment for refractory medial epicondylitis as demonstrated by a significant decrease in VAS pain and a fall in the modified Nirschl scores.
Birth and Evolutionary History of a Human Minisatellite
Authors: F. Boan
Journal: Molecular Biology and Evolution (2003)

One of the most exciting challenges in human biology is the understanding of how our genome was constructed during evolution. Here we explore the evolutionary history of the low polymorphic human minisatellite MsH42 and its flanking sequences. We show that the evolutionary birth of MsH42 took place within an intron, early in primate lineage evolution, more than 40 MYA. Then, single base-pair changes and duplications/deletions of repeat blocks by mispairing were probably the main forces governing the generation of this minisatellite and its polymorphism throughout primate evolution. Moreover, we detected several phylogenetic footprints at both sides of MsH42. We believe that our findings will contribute to the understanding of low-variability minisatellite evolution.
Effects of Asian Dust and Spherical Particles Exposure on Human Health and Allergic Symptom, Fukuoka, Japan
Authors: R.T. Kishikawa, T. Imai, T. Ichinose, Y. Okuno, K. Arashidani, M. Nishikawa, T. Shimoda, T. Iwanaga
Journal: Journal of Allergy and Clinical Immunology (2012)
Functionally Distinct Isoforms of STAT5 Are Generated by Protein Processing
Authors: Mohammad Azam, Carolyn Lee, Inga Strehlow, Christian Schindler
Journal: Immunity (1997)

The interleukin-3 family of cytokines, which play an important role in the development of myeloid lineages, transduce signals through the JAK–STAT pathway. Previous studies demonstrate that this process entails the activation of four distinct isoforms of STAT5, where two shorter isoforms are activated in a distinct population of cells. We now demonstrate that the shorter isoforms represent carboxy-terminal truncations. Moreover, these truncations are not generated by RNA processing, but by a specific proteolytic activity. Consistent with the notion that truncated STAT5 isoforms transduce distinct signals, they fail to promote the activation of several known interleukin-3 target genes. These studies suggest that the activity of a specific protease may play a critical role in defining the biological responses transduced by STAT5.
Making the Impossible Possible: Rooting the Tree of Placental Mammals
Authors: E. C. Teeling, S. B. Hedges
Journal: Molecular Biology and Evolution (2013)

Untangling the root of the evolutionary tree of placental mammals has been nearly an impossible task. The good news is that only three possibilities are seriously considered. The bad news is that all three possibilities are seriously considered. Paleontologists favor a root anchored by Xenarthra (e.g., sloths and anteater), whereas molecular evolutionists have favored the two other possible roots: Afrotheria (e.g., elephants, hyraxes, and tenrecs) and Atlantogenata (Afrotheria + Xenarthra). Now, two groups of researchers have scrutinized the largest available genomic data sets bearing on the question and have come to opposite conclusions, as reported in this issue of Molecular Biology and Evolution. Needless to say, more research is needed.
Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes
Authors: Patricia H. Gallego, Maria E. Craig, Anthony C. Duffin, Bruce Bennetts, Alicia J. Jenkins, Sabine Hofer, Albert Lam, Kim C. Donaghue
Journal: Diabetes Care (2008)

In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme. PON1 polymorphisms have been associated with susceptibility to macro- and microvascular complications. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants, p.Leu54Met, p.Gln192Arg, and c.-107C>T, in type 1 diabetes.This was a cross-sectional study of 331 adolescents with type 1 diabetes (162 male and 169 female). PFT was assessed by ultrasound, PON1 was assessed by genotyping with PCR and restriction fragment-length polymorphism, and serum PON1 activity was assessed by rates of hydrolysis of paraoxon and phenylacetate.Median (interquartile range) age was 15.4 (13.5-17.3) years, and diabetes duration was 7.6 (4.9-10.6) years. The distribution of p.Leu54Met genotypes was LL 135 (40.8%), ML 149 (45%), and MM 47 (14.2%). PFT was abnormal (>1.7 mm) in 159 adolescents (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL versus MM p.Leu54Met polymorphism (odds ratio 3.84 [95% CI 1.49-9.82], P = 0.005); BMI (percentile) (1.02 [1.01-1.03], P = 0.007); systolic blood pressure (percentile) (1.01 [1.00-1.02], P = 0.03); and male sex (3.29 [1.98-5.46], P < 0.001).Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with a reduced risk of abnormal PFT.
Diagnosing cystic fibrosis: what are we sweating about?
Authors: Nicholas J Simmonds, Andrew Bush
Journal: Thorax (2012)

Over the last few decades, the paradigm has shifted as cystic fibrosis (CF) is no longer a fatal disease of childhood and should be considered a chronic condition where survival into adulthood is expected. Median survival for current newborns is predicted to be at least 50 years and over 55% of patients in the UK are adults.1 Over these decades, our knowledge of the underlying pathophysiology has grown exponentially, from its original description in 1938 to the identification of the mutated gene ( cystic fibrosis transmembrane conductance regulator , CFTR ) in 1989.2 This has driven the development of effective therapies and brought about an increased understanding of the wide spectrum of diseases that result from abnormal CFTR function. During this time, the humble sweat test has remained at the heart of the diagnostic algorithm, with only modest changes from the original pilocarpine iontophoresis technique first described by Gibson and Cooke over half a century ago.3 Abnormal sweat electrolytes result from dysfunctional or absent CFTR protein in the epithelial cells of sweat glands.4 CFTR is widely distributed throughout the body and has many functions, such as encoding a cAMP-activated chloride channel and regulating transepithelial ion movement—a phenomenon identified by the measurement of potential difference across the nasal mucosa and later used as the basis of the nasal potential difference (NPD) diagnostic test.5 ,6

With the identification of the mutated gene and extensive knowledge of the associated basic defect, why is there still such a debate about the criteria for diagnosis and why do different diagnostic algorithms exist? When is CF atypical or non-classic and why introduce yet more terms—‘CFTR-related disorders’ and ‘CFTR-related metabolic syndrome’? Are these terms …
Lower Concentration of Thalamic<i>N</i>-Acetylaspartate in Patients With Schizophrenia: A Replication Study
Authors: Gabriele Ende, Dieter F. Braus, Sigrid Walter, Fritz A. Henn
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Using proton magnetic resonance spectroscopic imaging, the authors measured thalamic N-acetylaspartate (NAA) concentrations in patients with schizophrenia. METHOD: The study included 15 schizophrenic patients on a stable medication regimen and 15 age-matched healthy comparison subjects. Concentrations of NAA, creatine plus phosphocreatine, and choline-containing compounds in bilateral thalamic regions were determined. RESULTS: Previous findings of lower NAA concentration in the left and right mediodorsal region of the thalamus and significant correlations between left and right thalamic NAA measures in patients with schizophrenia were corroborated. Furthermore, the concentrations of choline-containing compounds were significantly lower in the schizophrenic patients. No group differences in creatine plus phosphocreatine were found. CONCLUSIONS: There is strong evidence for neuronal dysfunction or loss in the mediodorsal region of the thalamus in patients with schizophrenia.
Factors affecting radiographic progression of knee osteoarthritis.
Authors: J Ledingham, M Regan, A Jones, M Doherty
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVES--To evaluate the prognostic significance of patient characteristics and radiographic features at the knee for outcome of knee osteoarthritis. METHODS--This was a prospective observational study of 350 osteoarthritic knees. Clinical and radiographic data were obtained on 188 hospital referred patients (mean age 70, range 34-91 years). RESULTS--Median duration of follow up was two years (range 1-5 years). The majority of patients (48%) reported deterioration, but 23% experienced improvement in symptoms during the study period. Reported exercise tolerance remained unchanged in the majority (62%) and deteriorated in 35%. Change in at least one individual radiographic feature of osteoarthritis was seen in 252 (72%) knees: increase in joint space narrowing occurred in 52%, osteophyte in 32%, cysts in 19%, sclerosis in 14%, and attrition in 30%. Increase in Kellgren grade occurred in 137 (39%) knees. Knee effusion, osteoarthritis at multiple joint sites, and nodal change associated with change in Kellgren grade (odds ratios 1.03, 2.39, and 1.80; 95% confidence intervals (CI) 1.01 to 1.05, 1.16 to 4.93, and 1.02 to 3.17, respectively); warmth at the knee associated with change in any radiographic feature (odds ratio 2.22; 95% CI 1.19 to 4.14). Development of, or increase in, attrition and joint space narrowing associated with worsening symptoms and function and occurred with increased frequency in knees with effusions, clinical warmth and calcium pyrophosphate crystals in synovial fluid (p &lt; 0.05). CONCLUSIONS--A high rate of change, radiographic more than clinical, was seen in osteoarthritic knees during this study. Poor clinical and radiographic outcome associated with calcium pyrophosphate crystal deposition and clinical inflammation as reflected by knee effusion and warmth.
A Variant of the Transcription Factor 7-Like 2 (<i>TCF7L2</i>) Gene and the Risk of Posttransplantation Diabetes Mellitus in Renal Allograft Recipients
Authors: Eun Seok Kang, Myoung Soo Kim, Yu Seun Kim, Kyu Yeon Hur, Seung Jin Han, Chung Mo Nam, Chul Woo Ahn, Bong Soo Cha, Soon Il Kim, Hyun Chul Lee
Journal: Diabetes Care (2007)

Posttransplantation diabetes mellitus (PTDM) is a major complication associated with kidney transplantation. Defects in insulin secretion play a pivotal role in the pathogenesis of PTDM. A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene was reported to be associated with type 2 diabetes and possibly associated with an insulin secretion defect. The aim of this study was to investigate the association between genetic variations in TCF7L2 and PTDM in renal allograft recipients.A total of 511 unrelated renal allograft recipients without previously known diabetes were enrolled. Six single nucleotide polymorphisms (rs11196205, rs4506565, rs12243326, rs7903146, rs12255372, and rs7901695) were genotyped in the cohort, which consisted of 119 PTDM patients and 392 non-PTDM subjects. The genotyping of TCF7L2 polymorphisms was performed using real-time PCR.rs4506565, rs7901695, and rs7903146 were found to be in complete linkage disequilibrium. The rs7903146 genotype distribution was CC 94.3% and CT 5.7%. The incidence of PTDM was significantly higher in patients with the CT genotype than in patients with the CC genotype (41.4 vs. 22.2%) (odds ratio 2.474 [95% CI 1.146-5.341]; P = 0.024). The effect of this genotype remains significant after adjustment for age, sex, amount of body weight gain, and type of immunosuppressant (2.655 [1.168-6.038]; P = 0.020).These data suggest that the TCF7L2 rs7903146 genetic variation is associated with an increased risk of PTDM in renal allograft recipients.
Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation
Authors: Jack H. Crawford, T. Scott Isbell, Zhi Huang, Sruti Shiva, Balu K. Chacko, Alan N. Schechter, Victor M. Darley-Usmar, Jeffrey D. Kerby, John D. Lang, David Kraus, Chien Ho, Mark T. Gladwin, Rakesh P. Patel
Journal: Blood (2005)
Transmission of Severe Acute Respiratory Syndrome during Intubation and Mechanical Ventilation
Authors: Robert A. Fowler, Cameron B. Guest, Stephen E. Lapinsky, William J. Sibbald, Marie Louie, Patrick Tang, Andrew E. Simor, Thomas E. Stewart
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Nosocomial transmission of severe acute respiratory syndrome from critically ill patients to healthcare workers has been a prominent and worrisome feature of existing outbreaks. We have observed a greater risk of developing severe acute respiratory syndrome for physicians and nurses performing endotracheal intubation (relative risk [RR], 13.29; 95% confidence interval [CI], 2.99 to 59.04; p = 0.003). Nurses caring for patients receiving noninvasive positive-pressure ventilation may be at an increased risk (RR, 2.33; 95% CI, 0.25 to 21.76; p = 0.5), whereas nurses caring for patients receiving high-frequency oscillatory ventilation do not appear at an increased risk (RR, 0.74; 95% CI, 0.11 to 4.92; p = 0.6) compared with their respective reference cohorts. Specific infection control recommendations concerning the care of critically ill patients may help limit further nosocomial transmission.
Asynchronous Evolutionary Origins of A and BACE1
Authors: D. B. Moore, M. A. Gillentine, N. M. Botezatu, K. A. Wilson, A. E. Benson, J. A. Langeland
Journal: Molecular Biology and Evolution (2013)

Neurodegenerative plaques characteristic of Alzheimer's disease (AD) are composed of amyloid beta (Aβ) peptide, which is proteolyzed from amyloid precursor protein (APP) by β-secretase (beta-site APP cleaving enzyme [BACE1]) and γ-secretase. Although γ-secretase has essential functions across metazoans, no essential roles have been identified for BACE1 or Aβ. Because their only known function results in a disease phenotype, we sought to understand these components from an evolutionary perspective. We show that APP-like proteins are found throughout most animal taxa, but sequences homologous to Aβ are not found outside gnathostomes and the β cut site is only conserved within sarcopterygians. BACE1 enzymes, however, extend through basal chordates and as far as cnidaria. We then sought to determine whether BACE1 from a species that never evolved Aβ could proteolyze APP substrates that include Aβ. We demonstrate that BACE1 from a basal chordate is a functional ortholog that can liberate Aβ from full-length human APP, indicating BACE1 activity evolved at least 360 My before Aβ.
Surgical intervention for spontaneous hemothorax associated with neurofibromatosis type I
Authors: Ei Miyamoto, Hiroshi Hamakawa, Ichiro Sakanoue, Yutaka Takahashi
Journal: European Respiratory Journal (2013)

Rationale:

Neurofibromatosis type I (NF1) is a hereditary neurocutaneous syndrome resulted from the mutation in NF1 gene. The clinical diagnosis is comprehensively made by neurofibroma, Cafe-au-lait spot, osseous deformity and so on. Infrequently, aberrant neurofibromin function results in vasculopathy, which can cause fatal hemorrhage. However, it is unclear how surgical interventions should be made.

Case 1:

A 53-year-old man with NF1 was admitted for sudden chest pain. Computed tomography revealed left hemothorax and a tumorous aneurysm in the 7th intercostal artery. A thoracic drainage was performed immediately, and a thoracotomy was performed on 18 days after admission.

Case 2:

A 32-year-old man with NF1 was admitted due to chest back pain and hemodynamic instability. Computed tomography revealed left massive hemothorax and an extravasation from the 9th intercostal aneurysm. An urgent operation via left lateral thoracotomy was performed to remove hematoma and control active bleeding. On 7th postoperative day, the rerupture occurred and was treated with percutaneous transcatheter arterial embolism.

Discussion:

Management of fatal spontaneous hemothorax associated with NF1 depends on hemodynamic stability. According to 48 reported cases, intercostal and subclavian arteries are popular sites that burst. However, it is often difficult to control, and repeating rupture is known as a fatal complication. In the case 1, surgical intervention was put electively. On the other hand, it was urgently-required in the case 2. Thus, physician should be aware of the possibility of sudden-onset hemothorax in patients with NF1, and surgical intervention might play an important role to treat massive bleeding.
Structure and organization of the bovine beta-globin genes.
Authors: J C Schimenti, C H Duncan
Journal: Molecular Biology and Evolution (1985)

Genomic clones spanning the entire cow beta-globin gene locus have been isolated and characterized. These clones demonstrate that the linkage of embryonic-like (epsilon) genes and pseudogenes (psi) to the previously described fetal (gamma) and adult (beta) genes is as follows: 5'-epsilon 3-epsilon 4-psi 3-beta-epsilon 1-epsilon 2-psi 1-psi 2-gamma-3'. Present data indicate that, like that of the goat, the fetal and adult genes arose via block duplication of an ancestral four-gene set: epsilon-epsilon-psi-beta. This duplication event preceded the divergence of cows and goats, which occurred greater than or equal to 18-20 Myr ago. However, cows do not have the additional four-gene block containing a preadult/stress globin gene (beta C). Furthermore, the cow fetal cluster contains an extra beta-like pseudogene, which apparently arose by a small-scale duplication. The fixation of this duplication may indicate a possible evolutionary role for pseudogenes.