tbuckley/cabot-search huggingface dataset:
“The FSGS Factor”
Authors: MUKUT SHARMA, RAM SHARMA, ELLEN T. MCCARTHY, VIRGINIA J. SAVIN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. A circulating causative factor has been postulated in focal segmental glomerulosclerosis (FSGS). It has been shown that serum or plasma from some FSGS increases glomerular albumin permeability (P alb ) in vitro. P alb greater than 0.5 (i.e., FS activity) is associated with recurrence after transplantation. Specimens from 15 FSGS patients were studied to document the presence of a permeability factor, to isolate this factor, to characterize its biochemical properties, and to show its effect in vivo. Total lipids were extracted by chloroform/methanol (2:1); FS activity was absent from total lipid extract. Chylomicrons and lipoproteins were removed from the plasma with dextran sulfate, followed by sequential precipitation of proteins at 50 and 70% ammonium sulfate saturation. FS activity was retained in the 70% ammonium sulfate supernatant and exhibited a 100-fold purification. FS activity was lost after heating at 100°C for 10 min or after protease digestion. Under nondenaturing conditions, electrophoresis of the FSGS 70% supernatant showed a prominent low molecular weight band that was not evident in the 70% supernatant from normal plasma. Dialysis and centrifugation-based membrane ultrafiltration of the FSGS factor indicated a molecular size between 30 and 50 kD. Injection of the 70% FSGS supernatant into rats caused a threefold increase in urine protein in collections from 6 to 24 h after injection. No increase in proteinuria occurred in rats injected with 70% supernatant from normal individuals. It is concluded that the FSGS factor is a low molecular weight protein with the potential to increase P alb in vitro and to cause proteinuria in vivo.
Using a Mathematical Model in the Evaluation of Human Tumor Response to Chemotherapy&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Roger L. Priore
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Using a Mathematical Model in the Evaluation of Human Tumor Response to Chemotherapy Get access Roger L. Priore Roger L. Priore Department of Biostatistics, Roswell Park Memorial Institute, Buffalo, New York 14203 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 37, Issue 5, November 1966, Pages 635–647, https://doi.org/10.1093/jnci/37.5.635 Published: 01 November 1966 Article history Received: 31 March 1966 Published: 01 November 1966
Geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples in Croatia
Authors: Mateja Jankovic, Miroslav Samarzija, Sanja Popovic-Grle, Ivan Sabol, Mihaela Obrovac, Ljiljana Zmak, Gzim Redzepi, Vera Katalinic-Jankovic, Marko Jakopovic
Journal: European Respiratory Journal (2011)

Background:  The incidence of nontuberculous mycobacteria (NTM) as human pathogens is increasing. It has become clear that the NTM species obtained from clinical specimen differ strongly by region.   Aims and objectives: To determine the distribution of NTM species obtained from pulmonary samples of individuals from different geographic regions in Croatia.   Methods:  Retrospective analysis on all NTM identified at the National Laboratory for Mycobacteria in 2007-2009. For each isolate the person9s birth year, sex, specimen collection date, source and geographic region (costal or inland) were recorded. Microbiological criteria of the ATS/IDSA were used for a laboratory-based definition of pulmonary NTM.   Results:  NTM species were isolated from 712 individuals. 56% of isolates came from male (median age 62 y) and 44% from female (median age 64 years) individuals. More than two thirds of all isolates (525) originated from persons from the inland area. Out of those 525 samples, 80 (15.2%) met the pulmonary NTM criteria, compared to 68 (36.4%) out of the 187 samples identified in the costal area (p   Conclusions:  The majority of all NTM isolates originated from the inland area. However, isolates which met the ATS pulmonary disease criteria were more frequently isolated from persons living in the costal area. There, more than one third of all isolates likely represented true disease. Geographic region plays an important role for colonization or infection with NTMs in Croatia.
Activation of Ras by receptor tyrosine kinases.
Authors: B Margolis, E Y Skolnik
Journal: Journal of the American Society of Nephrology (1994)

Ras, a small GTP-binding protein, is an important component of the signal transduction pathway used by growth factors to initiate cell growth and differentiation. Cell activation with growth factors such as epidermal growth factor (EGF) induces Ras to move from an inactive GDP-bound state to an active GTP-bound state. Recently, a combination of genetic and biochemical studies has resulted in the elucidation of a signaling pathway that leads from growth factor receptors to Ras. After binding EGF, the EGF receptor tyrosine kinase is activated, leading to receptor autophosphorylation on multiple tyrosine residues. Signaling proteins with Src homology 2 (SH2) domains then bind to these tyrosine-phosphorylated residues, initiating multiple signaling cascades. One of these SH2 domain proteins, Grb2, exists in the cytoplasm in a preformed complex with a second protein, Son of Sevenless (Sos), which can catalyze Ras GTP/GDP exchange. After growth factor stimulation, the tyrosine phosphorylated EGF receptor binds the Grb2/Sos complex, translocating it to the plasma membrane. This translocation is thought to bring Sos into close proximity with Ras, leading to the activation of Ras. In contrast, the insulin receptor does not bind Grb2 directly but rather induces the tyrosine phosphorylation of two proteins, insulin receptor substrate-1 and Shc, that bind the Grb2/Sos complex. Once Ras is activated, it proceeds to stimulate a cascade of protein kinases that are important in a myriad of growth factor responses.
Immunocytochemical markers in stage I lung cancer: relevance to prognosis.
Authors: U Pastorino, S Andreola, E Tagliabue, F Pezzella, M Incarbone, G Sozzi, M Buyse, S Menard, M Pierotti, F Rilke
Journal: Journal of Clinical Oncology (1997)

PURPOSE This study investigated the frequency of the expression and prognostic significance of a panel of immunocytochemical markers in resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS A total of 515 cases of pathologic stage I NSCLC were analyzed. The median follow-up time of surviving patients was 102 months. The following immunocytochemical markers were tested: blood group A and precursors of blood antigens; laminin receptor; c-erbB1/epidermal growth factor receptor (EGFR) and c-erbB2/Neu; BCl2; p53; and angiogenesis. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical variables and biologic markers using the Cox model for multivariate analysis. RESULTS The pathologic tumor extension (pT) represented the most powerful prognostic factor for survival (P = .0008) and time to recurrence (P = .0007). None of the immunocytochemical markers emerged as an independent predictive factor for survival. Bcl2-positive tumors showed a better time to recurrence (P = .03), but the difference lost statistical significance in the multivariate analysis. Of interest, in the group of 137 patients classified as pT1N0, both EGFR expression and nonangiogenic type of vascular pattern were associated with a poorer survival (P = .02). However, data derived from subset analysis must be interpreted cautiously. CONCLUSION Our findings do not support a relevant prognostic role of immunocytochemical markers in NSCLC. The evidence is not sufficient to alter clinical practice or even to restrict clinical trials of adjuvant treatments to predefined biologic subsets of patients.
Late-breaking abstract: Demographic trends and changes In long term outcome of incident idiopathic, heritable and anorexigen-associated pulmonary arterial hypertension between 2001 to 2009. Results from the Pulmonary Hypertension Registry of the United Kingdom and Ireland
Authors: Yi Ling, Martin Johnson, David Kiely, Robin Condliffe, Charlie Elliot, Simon Gibbs, Luke Howard, Joanna Pepke-Zaba, Karen Sheares, Paul Corris, Andrew Fisher, Jim Lordan, Sean Gaine, Gerry Coghlan, John Wort, Michael Gatzoulis, Andrew Peacock
Journal: European Respiratory Journal (2011)

Background:  There have been significant changes in the management of pulmonary arterial hypertension (PAH) over the past decade. In the UK and Ireland, care of pulmonary hypertension (PH) is centralised to designated PH centres. This provides an excellent opportunity to study changes in demographic and survival trends of the disease within an entire region with a common healthcare system.   Aim:  To determine whether baseline characteristics and survival of  incident  IPAH, heritable and anorexigen-associated PAH has changed over the past decade.   Methods:  Retrospective observational study of all  incident  cases of IPAH, heritable and anorexigen-associated PAH diagnosed in the UK and Ireland between 1st January 2001 and 31st December 2009.   Results:  Total of 646 patients were diagnosed (22% in 2001-2003, 33% in 2004-2006 and 45% in 2007-2009). In recent years, patients were older, had higher BMI, lower % predicted diffusion capacity for carbon monoxide (DLCO) and had more co-morbidities (COPD, ischaemic heart disease and diabetes). There is no difference in unadjusted overall survival from 2001 to 2009. However, after adjusting for age, % DLCO, 6 minute walk distance and cardiac index, patients diagnosed in the 2001-2003 period were likely to have a shorter survival time compared to those diagnosed in 2007-2009 (hazard ratio 1.7, 95% CI 1.1-2.6)   Conclusion:  After adjusting for potential confounders, survival of  incident  IPAH, heritable and anorexigen-associated PAH in the UK and Ireland has improved over the last decade.
Book: Coping With Loss
Authors: M. Lloyd-Williams
Journal: BMJ (1999)

Ed Colin Murray Parkes, Andrew Markus BMJ Books, £14.95, pp168 ISBN 072791068X Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Doctors have largely replaced the village curate as the confidante of their patients' sorrows. Feelings of loss and the resulting distress—be it through bereavement or the break up of relationships —are therefore encountered more frequently by doctors. But how well equipped are we to deal with such patients, and how do we know when we have reached the ceiling of our competence? How do we cope with the continuous emotional pain of others and the pressures … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Late-breaking abstract: Why asthma still kills national review of asthma deaths (NRAD)
Authors: Mark Levy, Rachael Andrews, Rhona Buckingham, Hannah Evans, Rosie Houston, Navin Puri, Kevin Stewart
Journal: European Respiratory Journal (2014)

The UK NRAD, the largest prospective review of asthma deaths world wide, investigated 195 asthma deaths between February 2012 - January 2013.  Aim:  To identify potential avoidable factors and make recommendations to improve asthma care.  Method: 900 cases were selected from 3544 death certificates mentioning asthma; available data for 31%(276/900) of cases were included in the confidential enquiry. Median age of diagnosis and of death was 37 and 58 years respectively.  Results:  37 expert panels concluded that 71%(195/276) were asthma deaths and identified major potential avoidable factors in 67%(130); no record of personal asthma action plans (PAAPs) in 77%(151) of patients.  45%(87) died from asthma before medical assistance was sought or provided. 80%(8/10) of children and 72%(13/18) of young people, died before reaching a hospital.  The panels concluded that there was a failure to recognize and act on high-risk features of asthma attack and death, including excess prescription of reliever inhalers and low prescription of preventer inhalers. 10%(19) died within 28 days of hospital treatment for asthma attacks. 68%(13) of these had inadequate provision for discharge and follow-up. At least 21%(40) of those who died attended Emergency Departments at least once for asthma in the previous year.  58% of those who died were diagnosed as mild or moderately severe asthma. There was room for improvement/care was less than satisfactory in 83% (153/184) of cases.   The 19 NRAD recommendations included:  Assess asthma control and take appropriate action, PAAPs for all asthmatics, electronic prescribing alerts and research to determine whether late onset asthma is a risk factor for asthma death.
Cytotoxicity on Tumor Cells of Peripheral Blood Monocytes and Tumor-Associated Macrophages in Patients With Ascites Ovarian Tumors23
Authors: Alberto Mantovani, Nadia Polentarutti, Giuseppe Peri, Zvi Bar Shavit, Annunciata Vecchi, Giorgio Bolis, Costantino Mangioni
Journal: JNCI Journal of the National Cancer Institute (1980)

Mononuclear phagocytes were isolated from the peripheral blood (PB) and ascites tumors of 35 patients with epithelial ovarian tumors. After 48 hours of incubation with the TU5 tumor, tumor-associated macrophages (TAM) and PB monocytes from cancer patients showed lower cytolytic activity than did control cells, but by 72 hours there was little difference between control and ovarian cancer effector cells. Primary ovarian carcinoma cultures were heterogeneous in their susceptibility to macrophage cytotoxicity. Tumor cells from 7 patients were significantly lysed by monocytes and macrophages, whereas four ovarian cancer cell preparations were resistant to cytotoxicity. A "feeding" effect of mononuclear phagocytes on non-lysable tumor cells was detected in terms of both lower [3H]thymidine-release values in the cytolysis assay and increased proliferation in cytostasis assays. Thus patients with ovarian carcinomatous ascites PB monocytes and TAM had impaired cytotoxicity against a tumor cell line, and primary ovarian carcinoma cultures were heterogeneous in their interaction with mononuclear phagocytes.
Re-sequencing of PLAUR in severe asthma patients identifies novel variation
Authors: Michael Portelli, Nick Shrine, Yize Wan, Louise Wain, Tricia McKeever, Adel Mansur, Neil Thomson, Rekha Chaudhuri, Chris Brightling, A. Singapuri, Ian Hall, Ian Sayers
Journal: European Respiratory Journal (2014)

Background: We have previously identified that polymorphisms spanning the Urokinase Receptor Gene ( PLAUR ) are associated with asthma, decline in lung function and receptor levels. However, the variants driving genetic associations are not yet fully defined. Using next generation re-sequencing of the 19q13 region we aimed to identify common and rare variants differentially expressed in severe asthma and controls to bridge this gap in knowledge.

Method: 200 UK severe asthma patients (GINA ≥3) and 200 non-asthma/non-atopic controls were sequenced. Samples were multiplexed, with each group split into 3 pools ( n =66, 66 and 68). Target enrichment was carried out using the Agilent SureSelect kit (67.5kb region on 19q13). Paired-end sequencing was utilised and 100bp reads for cases and controls were run on the Illumina HiSeq2000™ System. Realignment around insertion deletions, recalibration of quality scores and variant detection were carried out using the GATK and Syzgy software packages. Data were compared to reference genome build 37.1.

Results: Mean coverage was 29x and 817 variants were identified, of which 399 (199 rare) were novel. In total, 12 exon variants were identified, with 2 novel rare variants in exons 1 and 6 predicted to cause functional changes to the uPAR protein sequence. Several variants were unique to cases or controls. On correcting for multiple testing, we identified 5 variants showing different representation in cases/controls. These variants were located upstream of PLAUR , with 4 variants forming a 7bp cluster of variation ∼23kb upstream of the start codon.

Conclusions: Re-sequencing PLAUR has identified novel common and rare variants that may be of relevance to asthma.
Anti-inflammatory effect of low dose theophylline in school children with bronchial asthma
Authors: Svetlana Kamenov, Aleksandar Kamenov, Snezana Cekic, Borislav Kamenov
Journal: European Respiratory Journal (2013)

Background: Treatment with theophylline is important with the patients suffering from moderate bronchial asthma. Few studies have shown that the late asthmatic response to an allergen challenge is inhibited by theophylline.  Methods: The objective of the research work is to point whether a low dose of theophylline has anti-inflammatory effect in asthma. We have analyzed a group of 30 asthmatic school children for 8 weeks. They received 125 mg theophylline twice daily. In all patients FEV1, symptom score, and reduction of the eosinophil number in the peripheral blood were determined.  Results: After the treatment we noticed an increase of values of FEV1 from (71± 3.2) to (96± 2.1) improving symptom score (p  Conclusion: During the treatment improvement of symptoms and lung function were noticed. Low dose theophylline is safe and has inhibitory effect on airway inflammation.
Recurrent Epithelial Ovarian Carcinoma: A Randomized Phase III Study of Pegylated Liposomal Doxorubicin Versus Topotecan
Authors: Alan N. Gordon, John T. Fleagle, David Guthrie, David E. Parkin, Martin E. Gore, Angel J. Lacave
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To compare the efficacy and safety of pegylated liposomal doxorubicin (PLD) and topotecan in patients with epithelial ovarian carcinoma that recurred after or didn’t respond to first-line, platinum-based chemotherapy. PATIENTS AND METHODS: Patients with measurable and assessable disease were randomized to receive either PLD 50 mg/m 2 as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m 2 /d for 5 consecutive days every 3 weeks. Patients were stratified prospectively for platinum sensitivity and for the presence or absence of bulky disease. RESULTS: A total of 474 patients were treated (239 PLD and 235 topotecan). They comprised the intent-to-treat population. The overall progression-free survival rates were similar between the two arms (P = .095). The overall response rates for PLD and topotecan were 19.7% and 17.0%, respectively (P = .390). Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan. Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival (P = .037), with medians of 28.9 for PLD versus 23.3 weeks for topotecan. For overall survival, PLD was significantly superior to topotecan (P = .008), with a median of 108 weeks versus 71.1 weeks. The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan (P = .455). Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification, or growth factor or blood product utilization. CONCLUSION: The comparable efficacy, favorable safety profile, and convenient dosing support the role of PLD as a valuable treatment option in this patient population.
Vitamin C and the Common Cold.
Authors: Linus Pauling
Journal: Annals of Internal Medicine (1972)

Huge doses of vitamin C, from one to ten grams daily, are recommended by some scientists as a treatment for and preventative against the common cold. But the prolonged use of such large doses may be dangerous, because there is evidence that breakdown products of vitamin C formed in the body (for instance, oxalic acid) are a threat to health. Also large doses of the vitamin can enhance the dangerous effects of certain toxic substances in food. It would obviously be both easier and safer for the public to take vitamin C in the smaller quantities in which it is found in certain foodstuffs. Citrus fruits, such as oranges and lemons and also blackcurrants, are particularly rich in vitamin C, the average orange containing about 30mg.
Lung function decline in adult asthmatics. A 10-year follow-up
Authors: Giuseppina Cuttitta, Salvatore Bucchieri, Fabio Cibella, Mario Melis, Giovanni Viegi
Journal: European Respiratory Journal (2012)

Conflicting results exist regarding the rate of lung function decline in asthmatics. We evaluated the longitudinal changes in FEV1 in asthmatic outpatients during a 10-year follow-up comparing the 1st period (years 1-5) with the 2nd period (years 6-10) also identifying factors affecting changes in functional decline. We studied 105 asthmatics (45 M, aged 18-76 years) with clinical and functional asthma diagnosis. Spirometry was performed every 3 months. FEV1 variability at the 1st year was computed. Short term treatments with oral steroids (OS) were used as needed. The best FEV1 measures at 1st, 5th and 10th year were evaluated and normalized for the subject's height at third power (FEV1/Ht3). The slopes FEV1/Ht3 vs time during the 1st and 2nd periods were evaluated. We evaluated the effect of body mass index, baseline FEV1, age at enrolment, age of disease onset, disease duration, allergic sensitization, number of OS courses, and FEV1 variability on FEV1 decay slopes. Median FEV1/Ht3 slope values were -.013 and -.006 (l/m3/year) for the 1st and 2nd period, respectively (p<0.0001). No correlation was found between the slopes of the two periods. 1st period slopes were correlated to FEV1 variability (p<0.0001), but such correlation was not found for 2nd period slopes. Negative relationship between 1st period slopes and long term reversibility was found (p=0.006). Subjects with disease duration≤5 years had steeper 1st period slopes (p=0.04). A relationship was found between 1st period slopes and the number of OS courses (p=0.002). In conclusion, FEV1 decay in treated adult asthmatics is not constant. In particular, it slows down over time, and is influenced by some subjects' clinical and functional characteristics.
Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop
Authors: Elizabeth Haney, M.E. Beth Smith, Marian McDonagh, Miranda Pappas, Monica Daeges, Ngoc Wasson, Heidi D. Nelson
Journal: Annals of Internal Medicine (2015)

The diagnosis of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is based on clinical criteria, yet there has been no consensus regarding which set of criteria best identifies patients with the condition. The Institute of Medicine has recently proposed a new case definition and diagnostic algorithm.To review methods to diagnose ME/CFS in adults and identify research gaps and needs for future research.MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; and reference lists.English-language studies describing methods of diagnosis of ME/CFS and their accuracy.Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria, and discrepancies were resolved through consensus.Forty-four studies met inclusion criteria. Eight case definitions have been used to define ME/CFS; a ninth, recently proposed by the Institute of Medicine, includes principal elements of previous definitions. Patients meeting criteria for ME represent a more symptomatic subset of the broader ME/CFS population. Scales rating self-reported symptoms differentiate patients with ME/CFS from healthy controls under study conditions but have not been evaluated in clinically undiagnosed patients to determine validity and generalizability.Studies were heterogeneous and were limited by size, number, applicability, and methodological quality. Most methods were tested in highly selected patient populations.Nine sets of clinical criteria are available to define ME/CFS, yet none of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. More definitive studies in broader populations are needed to address these research gaps.