tbuckley/cabot-search huggingface dataset:
Dissecting “PI3Kness”: The Complexity of Personalized Therapy for Ovarian Cancer
Authors: Robert C. Bast, Gordon B. Mills
Journal: Cancer Discovery (2012)

Abstract Epithelial ovarian cancers exhibit marked heterogeneity and can be divided into low-grade type I and more prevalent high-grade type II lesions that differ in stage at diagnosis, rate of growth, and susceptibility to platinum-based chemotherapy. Activation of the phosphatidylinositol 3′ kinase (PI3K) pathway occurs in a significant fraction of both types of ovarian cancer, driven predominantly by mutations in type I and amplification in type II. Available cell lines do not often reflect the genotype of type II ovarian cancers, but studies with cell lines driven by mutation suggest that blocking activated AKT is necessary, but not sufficient to inhibit cancer cell growth. Inhibition of multiple signaling pathways will likely be required to achieve effective personalized therapy for patients whose cancers exhibit “PI3Kness.” Cancer Discovery; 2(1); 16–8. ©2012 AACR. Commentary on Hanrahan et al., p. 56.
Serum α-1 Proteinase Inhibitor in Advanced Cancer: Mass Variants and Functionally Inert Forms
Authors: Rajender K. Chawla, David H. Lawson, P. Ravi Sarma, Daniel W. Nixon, James Travis
Journal: Cancer Research (1987)

In 1984, we reported that while immunoreactive levels of serum α-1 proteinase inhibitor (API) increased significantly in nine patients with advanced solid tumors, the functional activity of the inhibitor, as measured by the serum trypsin inhibitory capacity, did not increase proportionately. This suggested that a portion of the circulating API was functionally inert. We have now assayed immunoreactive titers and trypsin inhibitory capacity of serum API of 49 patients with advanced carcinomas and 27 healthy controls. Immunoreactive levels of API (expressed as percentage of normal pooled serum which was taken as 100%) in cancer subjects were significantly elevated as compared to normals (mean ± SE: 233 ± 9.0% versus 102 ± 2.0%, P < 0.05). Although the trypsin inhibitory capacity of the cancer group (16.0 ± 0.9 units/ml) was significantly elevated ( P < 0.05) as compared to normals (9.9 ± 0.1 units/ml), this increase was less than that in the immunoreactive titer of API, suggesting the existence of functionally inert API in serum. The fraction of API which was functionally active in this group of cancer patients was 71.0 ± 3.0% which was significantly less than the normal 98.0 ± 2.0% ( P < 0.05). In 12 patients followed serially, both immunoreactive levels of API and the trypsin inhibitory capacity increased significantly at the time of clinical progression of disease. There was a significant correlation between increasing absolute granulocyte count and increasing trypsin inhibitory capacity (correlation coefficient 0.66; P < 0.001). Neither disease progression nor increasing granulocyte count, however, was associated with increasing proportion of functionally inactive API. The inactive from of API had the same molecular weight as the native molecule as shown by gel permeation chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis of cancer sera. Therefore, the inactive form was not due to a complex between API and a tumor-derived protease or to proteolytic fragmentation of the native API. Elastase inhibitory capacity of cancer sera with subactive API was essentially identical with trypsin inhibitory capacity indicating that the active site methionine was not oxidized in the inert API. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis showed that both normal and cancer serum API existed as two mass variants, at M r 58,000 and 56,000. Both variants formed complexes with elastase and were functionally active.
Use of biological glue to control pulmonary air leaks.
Authors: A F Matar, J G Hill, W Duncan, N Orfanakis, I Law
Journal: Thorax (1990)

Biological glue is a natural adhesive generated by the interaction between fibrinogen (pre-glue) and thrombin to produce fibrin. The pre-glue is prepared from a single donor (to avoid the problems of pooled plasma) and stored as cryoprecipitate. Before being used it is thawed, dissolved in saline, and activated into an adhesive by the addition of topical thrombin. Biological glue was used prophylactically to prevent air leaks from bronchial suture lines and raw lung surfaces after pulmonary resections in six patients. In addition two new methods of using biological glue have been developed for the control of persisting air leaks. In selective intrabronchial tamponade the glue is instilled into the bronchial tree through a flexible bronchoscope, and in therapeutic pleurodesis it is instilled into the pleural cavity through a chest drainage tube. The air leaks were resolved in all cases. Seven procedures using selective intrabronchial tamponade were carried out in six patients. Four were immediately successful but three were not and required further interventions. Therapeutic pleurodesis alone was successfully carried out in one patient and as an adjunct to selective intrabronchial tamponade on two occasions. A thoracotomy was eventually needed in one of the seven patients.
Induction of monocyte chemoattractant protein-1 in proximal tubule cells by urinary protein.
Authors: Y Wang, J Chen, L Chen, Y C Tay, G K Rangan, D C Harris
Journal: Journal of the American Society of Nephrology (1997)

Cytokines play a pivotal role in synthesis and deposition of extracellular matrix in chronic renal failure (CRF). The proinflammatory properties of monocyte chemoattractant protein (MCP)-1 make it an ideal candidate cytokine for the production of interstitial inflammation in CRF. To investigate the possible role of proteinuria in inducing proximal tubular (PT) MCP-1, MCP-1 mRNA levels were measured by Northern blot and reverse transcription PCR in confluent monolayers of PT cells in primary culture in media containing a variety of proteins. PT cells produced MCP-1 mRNA in response to bovine serum albumin (BSA), delipidated BSA (dBSA; 0.5 to 30 mg/ml), holotransferrin, and apotransferrin (1 to 8 mg/ml). Unstimulated PT cells expressed very low levels of MCP-1 mRNA, detectable by reverse transcription PCR but not by Northern blot. The expression of MCP-1 mRNA reached a peak (sixfold greater than control) within 4 h of exposure to dBSA and was maintained for at least 24 h with continued exposure. Removal of dBSA from the media led to a rapid decline in MCP-1 mRNA expression. dBSA-induced MCP-1 expression was inhibited by lysine, an inhibitor of protein uptake, and reproduced by dBSA purified by gel and size-selective filtration. dBSA influenced MCP-1 expression at the level of transcription and probably translation, as evidenced by abrogation of MCP-1 by actinomycin D and superinduction with the protein synthesis inhibitor cycloheximide. The concentration of MCP-1 protein in response to dBSA added to the apical surface of PT cells was 2.4-fold greater in basolateral than in apical media, indicating basolateral secretion of MCP-1 protein. In summary, PT cell MCP-1 mRNA and protein expression are upregulated by albumin and transferrin, in concentrations similar to those of proteinuric urine. This effect could explain the link between proteinuria and interstitial inflammation in CRF.
Effectiveness of intra-articular hyaluronan (Synvisc, hylan G-F 20) for the treatment of first metatarsophalangeal joint osteoarthritis: a randomised placebo-controlled trial
Authors: Shannon E Munteanu, Gerard V Zammit, Hylton B Menz, Karl B Landorf, Christopher J Handley, Ayman Elzarka, Jason DeLuca
Journal: Annals of the Rheumatic Diseases (2011)

Objectives To evaluate the effectiveness of a single intra-articular injection of hylan G-F 20 (Synvisc) for symptomatic first metatarsophalangeal joint (MTPJ) osteoarthritis (OA). Methods Participants (n = 151) with symptomatic first MTPJ OA were randomly allocated to receive up to 1 ml intra-articular injection of either hylan G-F 20 or placebo (saline). Participants and assessors were blinded. Outcomes were evaluated at 1, 3 and 6 months after injection. The primary outcome measurement was the foot pain domain of the Foot Health Status Questionnaire (FHSQ) at 3 months. Secondary outcome measurements were foot function assessed via the FHSQ, first MTPJ pain and stiffness, magnitude of symptom change, global satisfaction, health-related quality of life (assessed using the Short-Form-36 version two), first MTPJ dorsiflexion range of motion, hallux plantar flexion strength, use of pain-relieving medication or co-interventions and changes in plantar pressures. Results No statistically significant differences in foot pain were found between the groups at 3 months. There were few statistically significant differences in the secondary outcome measures. Overall, the incidence of adverse effects was not significantly different between groups. Conclusions An intra-articular injection of hylan G-F 20 is no more effective than a placebo in reducing symptoms in people with symptomatic first MTPJ OA.Australian New Zealand Clinical Trials Registry: number ACTRN12607000654459.
The Potential Effect of Some Newer Risk Factors for Atherosclerosis on Aortic Distensibility in Subjects With and Without Type 2 Diabetes
Authors: Athanasia Papazafiropoulou, Nicholas Tentolouris, Ioannis Moyssakis, Despoina Perrea, Nicholas Katsilambros
Journal: Diabetes Care (2006)

The classical cardiovascular risk factors explain only a part of the increased macrovascular disease in subjects with type 2 diabetes (1). Reduction of the elastic properties of the aorta is an early marker of atherosclerosis, and it is diagnosed early in the course of type 2 diabetes (2). The detrimental effects of the classical risk factors on aortic distensibility are well known. However, the potential effect of some newer markers that have been proposed as risk factors for atherosclerosis, including increased plasma homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and uric acid levels, increased white blood cell (WBC) count, and low plasma adiponectin levels on aortic distensibility, has not been studied so far. The present cross-sectional study deals with the effect of the classical and newer cardiovascular risk factors on aortic distensibility in subjects with and without type 2 diabetes.

We studied 100 subjects (49 male and 51 female, mean age 59.4 ± 1.0 years, duration of diabetes 9.8 ± 7.1 years) with type 2 diabetes consecutively attending the outpatient diabetes clinic of our hospital. In addition, 100 subjects (49 male and 51 female, aged 59.2 ± 1.0 years) without diabetes who had attended the hospital for minor problems were also recruited. Type 2 diabetes was diagnosed according to the American Diabetes Association criteria (3). Subjects with clinically apparent macrovascular disease and renal impairment were excluded.

Blood was collected after an overnight fast of at least 12 h. Plasma glucose, lipids, HbA1c (A1C), creatinine, …
Maternal and Fetal Factors Associated With Mortality and Morbidity in a Multi–Racial/Ethnic Registry of Anti-SSA/Ro–Associated Cardiac Neonatal Lupus
Authors: Peter M. Izmirly, Amit Saxena, Mimi Y. Kim, Dan Wang, Sara K. Sahl, Carolina Llanos, Deborah Friedman, Jill P. Buyon
Journal: Circulation (2011)

Background— Cardiac manifestations of neonatal lupus include conduction disease and, rarely, an isolated cardiomyopathy. This study was initiated to determine the mortality and morbidity of cardiac neonatal lupus and associated risk factors in a multi–racial/ethnic US-based registry to provide insights into the pathogenesis of antibody-mediated injury and data for counseling. Methods and Results— Three hundred twenty-five offspring exposed to maternal anti-SSA/Ro antibodies with cardiac neonatal lupus met entry criteria. Maternal, fetal echocardiographic, and neonatal risk factors were assessed for association with mortality. Fifty-seven (17.5%) died, 30% in utero. The probability of in utero death was 6%. The cumulative probability of survival at 10 years for a child born alive was 86%. Fetal echocardiographic risk factors associated with increased mortality in a multivariable analysis of all cases included hydrops and endocardial fibroelastosis. Significant predictors of in utero death were hydrops and earlier diagnosis, and of postnatal death were hydrops, endocardial fibroelastosis, and lower ventricular rate. Isolated heart block was associated with a 7.8% case fatality rate, whereas the concomitant presence of dilated cardiomyopathy or endocardial fibroelastosis quadrupled the case fatality rate. There was a significantly higher case fatality rate in minorities compared with whites, who were at a lower risk of hydrops and endocardial fibroelastosis. Pacing was required in 70%; cardiac transplantation was required in 4 children. Conclusion— Nearly one fifth of fetuses who develop cardiac neonatal lupus die of complications predicted by echocardiographic abnormalities consistent with antibody-associated disease beyond the atrioventricular node. The disparity in outcomes observed between minorities and whites warrants further investigation.
Twelve-month health related quality of life and functional outcomes of hospitalised orthopaedic sport and active recreation injuries
Authors: N Andrew, B J Gabbe, R Wolfe, P A Cameron
Journal: British Journal of Sports Medicine (2011)

Background Serious sport and active recreation injuries are common with the potential for grave long-term consequences. Despite this few studies have examined the long-term outcomes of these injuries. Objective To establish if patients hospitalised with orthopaedic sport and active recreation injuries have returned to their pre-injury levels of health and function 12-months post-injury and to identify predictors of poor outcomes. Design Prospective cohort study with 12-month follow-up. Setting Two Level 1 trauma centres and one regional hospital in Victoria, Australia. Participants Adults with orthopaedic sport and active recreation injuries who were admitted to either Level 1 trauma centre between March 2008 and March 2009 or the regional hospital between June 2008 and June 2009 and captured by the Victorian Orthopaedic Trauma Outcomes Registry. There were 324 participants recruited to the study of which 98% were successfully followed up at 12-months post-injury. Assessment of risk factors Independent variables assessed for predictors of outcome were sporting group, age, sex, education level, major trauma classification (injury severity score&gt;15) and injury patterns. Main outcome measurements The 36-item Short Form Health Survey (SF-36) and the Glasgow Outcome Scale Extended. Results At 12-months post-injury 58.1% of participants reported reduced function and a significant reduction in physical health (p&lt;0.001) and mental health (p&lt;0.001). Multivariate analysis identified injury due to motor sports (p=0.001) or equestrian sports (p=0.015) and being classified as a major trauma (p=0.043), as predictors of a poor physical health outcome. Low education level (p=0.040) and having a major trauma injury (p=0.047) were predictors of a poor mental health outcome. Conclusion The findings of our study highlight that at 12-month post-injury, most patients injured during sport and active recreation had not returned to their pre-injury status. This information is useful for setting priorities for treatment and for the progression of sports injury prevention.
Quantification of the dose of inhaled flour: relation with nonspecific bronchial and immunological reactivities
Authors: D Choudat, JF Fabries, JC Martin, C Villette, F Tabka, JF Dessanges, JD Ava, F Conso
Journal: European Respiratory Journal (1999)

The aim of this study was to investigate the relationship between specific bronchial reactivity and respective nonspecific bronchial and immunological reactivities. Twenty-one patients underwent bronchial challenges with lactose and flour. The aerosol of particles was generated by a computer-controlled aerosolizer. Specific bronchial challenge results were expressed as the provocative dose of flour (PDf) that caused a 20% or 15% decrease in the forced expiratory volume in one second (FEV1). For each subject, the decrease in FEV1 observed during the challenge with flour was compared with the calculated lower limit of the 99.7% confidence interval for the lactose challenge. The subjects also underwent a nonspecific challenge with methacholine and a measurement of the specific immunoglobulin E against wheat. The inhalation of lactose did not significantly affect FEV1. Nine subjects had high reactivity to wheat flour with a PDf20 &lt;400 microg. Five subjects had intermediate reactivity: FEV1 fell by &lt;20% but by significantly more than that in the test with lactose. For 7 subjects, there was no significant change in FEVI for inhaled doses of flour over 1390 microg. The results for specific bronchial challenge were significantly correlated with those for the methacholine test (p&lt;0.02). Positive skin tests and specific immunoglobulin E against wheat were observed more frequently in the high reactivity group. Specific bronchial challenge can be performed safely to establish precise dose-response curves. The provocative dose of flour causing a 20% decrease in forced expiratory volume in one second is useful for evaluating the degree of specific reactivity but is not suitable in cases of intermediate reactivity in which comparison with the lactose test is necessary. Specific reactivity is probably a function of immunological and nonspecific bronchial reactivities.
Platelet satellitism and phagocytosis by neutrophils: Association with antiplatelet antibodies and lymphoma
Authors: Leonard A. White, Leonard H. Brubaker, Richard H. Aster, Patrick H. Henry, Edward H. Adelstein
Journal: American Journal of Hematology (1978)

Abstract Satellitism and phagocytosis of platelets by neutrophils in EDTA anticoagulated blood have been considered in vitro phenomena without clinical significance. We observed these in a patient with acute, severe thrombocytopenic purpura who subsequently proved to have malignant lymphoma. Wide oscillations in the platelet count were noted and recurrent, severe gastrointestinal bleeding occurred even when the platelet count was normal. Platelet function was abnormal as shown by decreased platelet adhesion to glass beads, absence of a secondary wave of aggregation in response to ADP and epinephrine, and no aggregation with collagen. Suspension of control platelets in the patient's plasma induced similar aggregation defects in the control platelets. Combination chemotherapy resulted in regression of lymphadenopathy, but platelet abnormalities and bleeding persisted. Platelet satellitism and phagocytosis by neutrophils seen on peripheral blood films may be associated with true thrombocytopenia, abnormal platelet function and bleeding with an underlying systemic disease.
Frontiers in pruritus research: scratching the brain for more effective itch therapy
Authors: R. Paus
Journal: Journal of Clinical Investigation (2006)

This Review highlights selected frontiers in pruritus research and focuses on recently attained insights into the neurophysiological, neuroimmunological, and neuroendocrine mechanisms underlying skin-derived itch (pruritogenic pruritus), which may affect future antipruritic strategies. Special attention is paid to newly identified itch-specific neuronal pathways in the spinothalamic tract that are distinct from pain pathways and to CNS regions that process peripheral pruritogenic stimuli. In addition, the relation between itch and pain is discussed, with emphasis on how the intimate contacts between these closely related yet distinct sensory phenomena may be exploited therapeutically. Furthermore, newly identified or unduly neglected intracutaneous itch mediators (e.g., endovanilloids, proteases, cannabinoids, opioids, neurotrophins, and cytokines) and relevant receptors (e.g., vanilloid receptor channels and proteinase-activated, cannabinoid, opioid, cytokine, and new histamine receptors) are discussed. In summarizing promising new avenues for managing itch more effectively, we advocate therapeutic approaches that strive for the combination of peripherally active antiinflammatory agents with drugs that counteract chronic central itch sensitization.
Involuntary Hospitalization: What For and How Long?
Authors: JAMES SPENSLEY, JAMES T. BARTER, PAUL H. WERME, DONALD G. LANGSLEY
Journal: American Journal of Psychiatry (1974)

In spite of much criticism of the practice of involuntary hospitalization for mental illness, specific data on the practice are lacking. This study examined the data on all involuntarily hospitalized patients (N = 226) discharged from Sacramento Medical Center in 1971. The results showed that the median length of involuntary stay was short (three days), the majority of patients accepted a recommendation for voluntary outpatient treatment, and lengthy involuntary treatment was rarely needed. In California the civil rights of such patients are protected by a system of periodic review of each case by the courts.
Sport injuries of the elbow
Authors: S P Frostick, M Mohammad, D A Ritchie
Journal: British Journal of Sports Medicine (1999)

Athletic injuries of the elbow are common especially in throwing sports such as baseball and tennis. An early diagnosis, early initiation of treatment, and appropriate referrals for surgical management enable athletes to return safely to competition as quickly as possible. Elbow injuries may involve any of the anatomical structures in the region. The normal range of motion at the elbow joint is 140° of flexion from full extension and from 75° of pronation to 85° of supination. The functional range of motion for activities of daily living is from 30° to 130° of flexion and 50° of supination and pronation. This arc of motion allows independent function but would be very limiting for many athletic pursuits. The most appropriate range of motion varies with the type of sport. For example, a gymnast performing handstands requires at least full extension (if not hyperextension) to lock the elbows, whereas baseball pitchers may have a flexion contracture of their dominant elbow of up to 20° that does not limit their eVectiveness. Elbow injuries in athletes can be classified into acute or chronic. Most injuries in the athlete are chronic overuse injuries. Overuse injuries are the result of repetitive overload resulting in microtears of the soft tissues. They are often myotendinous to the flexor-pronator muscle group and can lead to tendonitis or muscular injury and eventually elbow flexion contracture. Repetitive microrupture of the flexor-pronator muscle group compromises the healing process leading to muscle contracture and fatigue. More repetitive stresses to the ulnar side of the elbow aVect the ulnar collateral ligament. Imperfect healing of the medial collateral ligament (MCL) results in its attenuation and elbow instability. Any further valgus stresses induce compression of the radiocapitellar joint.