tbuckley/cabot-search huggingface dataset:
Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review
Authors: Charles Gyamera-Acheampong, Majambu Mbikay
Journal: Human Reproduction Update (2008)

BACKGROUNDProprotein convertase subtilisin/kexin type 4 (PCSK4), also known as proprotein convertase 4, belongs to a family of endoproteinases involved in the proteolytic conversion of secretory precursor proteins to their active forms. Its amino acid sequence is highly conserved in mammals, an indication of its biological importance.
Basophils Produce IL-4 and Accumulate in Tissues after Infection with a Th2-inducing Parasite
Authors: Booki Min, Melanie Prout, Jane Hu-Li, Jinfang Zhu, Dragana Jankovic, Ellen S. Morgan, Joseph F. Urban, Ann M. Dvorak, Fred D. Finkelman, Graham LeGros, William E. Paul
Journal: The Journal of Experimental Medicine (2004)

Using mice in which the eGfp gene replaced the first exon of the Il4 gene (G4 mice), we examined production of interleukin (IL)-4 during infection by the intestinal nematode Nippostrongylus brasiliensis (Nb). Nb infection induced green fluorescent protein (GFP)pos cells that were FcεRIpos, CD49bbright, c-kitneg, and Gr1neg. These cells had lobulated nuclei and granules characteristic of basophils. They were found mainly in the liver and lung, to a lesser degree in the spleen, but not in the lymph nodes. Although some liver basophils from naive mice express GFP, Nb infection enhanced GFP expression and increased the number of tissue basophils. Similar basophil GFP expression was found in infected Stat6−/− mice. Basophils did not increase in number in infected Rag2−/− mice; Rag2−/− mice reconstituted with CD4 T cells allowed significant basophil accumulation, indicating that CD4 T cells can direct both tissue migration of basophils and enhanced IL-4 production. IL-4 production was immunoglobulin independent and only partially dependent on IL-3. Thus, infection with a parasite that induces a “Th2-type response” resulted in accumulation of tissue basophils, and these cells, stimulated by a non-FcR cross-linking mechanism, are a principal source of in vivo IL-4 production.
Correlation of fatty acid composition of adipose tissue lipids and serum phosphatidylcholine and serum concentrations of micronutrients with disease duration in rheumatoid arthritis.
Authors: L Jacobsson, F Lindgärde, R Manthorpe, B Akesson
Journal: Annals of the Rheumatic Diseases (1990)

To establish the concentrations of micronutrients in serum, fatty acid composition in serum phosphatidylcholine and in adipose tissue, and their correlation with inflammation and disease duration in rheumatoid arthritis (RA), 21 consecutive patients with recently diagnosed disease (mean duration eight months), 21 patients with longstanding disease (mean duration 15 years), and 57 controls were examined. In the patients with RA low concentrations of the essential fatty acids, linoleic acid (18:2) and linolenic (18:3) acid, and high concentrations of total saturated fatty acids, both in serum phosphatidylcholine and in adipose tissue, were found, abnormalities that increased with disease duration. The proportion of 18:2 in serum phosphatidylcholine correlated inversely with such acute phase proteins as orosomucoid and C reactive protein. It is proposed that the decreases in essential fatty acids are related to increased activity in the desaturase/elongation enzymes, increased production of eicosanoids, or metabolic changes secondary to cytokine mediated inflammatory reaction. When the micronutrients were studied it was found that serum concentrations of selenium were lower in patients than in controls, but not those of ascorbic acid, alpha-tocopherol, retinol, folic acid, or cobalamine. Ascorbic acid concentrations tended to be lower in RA, however, and correlated inversely with those of haptoglobin, orosomucoid, and C reactive protein, indicating a relation between the ascorbic acid concentration and the degree of inflammation.
No reliable evidence that folate is harmful in B-12 deficiency
Authors: C J. Dickinson
Journal: BMJ (1995)

Mental Health Act 1983 would be a standard course of action if he or she refused voluntary admission.It is wrong to suggest that if such a patient took an overdose his or her refusal of treatment while distressed should be considered to be valid.In most cases of self poisoning presenting to casualty departments the history is scanty, the patient is uncooperative, and treatment is needed immediately.If fleeting refusals of treatment were to be honoured many lives would negligently be lost; this is not what English law requires of doctors.The common law allows doctors to act in the best interests of patients if they do not have the capacity to consent.
HIV in Africa
Authors: E S. Sills, R. J C Young
Journal: Journal of the Royal Society of Medicine (2003)

We agree with Mr Loefler (October 2002, JRSM1) that the HIV disaster has special dimensions in Africa. He contends that ‘a change in socioeconomic conditions’ is needed to address the pandemic, and accordingly offers a general prescription for ending the postcolonial status of Africa as an exploited society. The implementation of less philosophical responses by organizations such as Global Strategies for HIV Prevention and AMREF by contrast have already registered substantial accomplishments in curbing this disease. One nevirapine tablet given during labour and delivery (followed by a single dose of nevirapine syrup to baby) reduces vertical HIV transmission by 50%. In Tanzania, for example, other multifaceted prevention and treatment approaches have already shown promise by explicitly addressing gender issues that propel the HIV epidemic. Working to make practical programmes such as these function better and reach more people will add considerably to the fight against HIV in Africa, and elsewhere.

When a senior African physician laments ‘I know of no medical school in Africa that teaches medical care appropriate to the circumstances in the country’2, then non-Africans will question why this state prevails there. If it is the case that self-determination has taken African medical schools down a path of medical irrelevancy, then the HIV problem is made needlessly complex. Accordingly, Loefler and other leading African scholars may wish to focus more energy on repairing the local medical education dysfunctions in Africa and on supporting programmes with proven track records in the fight against HIV, rather than on inventing a new world order. Which goals are more likely to be achieved?
Parallel Histories of Horizontal Gene Transfer Facilitated Extreme Reduction of Endosymbiont Genomes in Sap-Feeding Insects
Authors: Daniel B. Sloan, Atsushi Nakabachi, Stephen Richards, Jiaxin Qu, Shwetha Canchi Murali, Richard A. Gibbs, Nancy A. Moran
Journal: Molecular Biology and Evolution (2014)

Bacteria confined to intracellular environments experience extensive genome reduction. In extreme cases, insect endosymbionts have evolved genomes that are so gene-poor that they blur the distinction between bacteria and endosymbiotically derived organelles such as mitochondria and plastids. To understand the host’s role in this extreme gene loss, we analyzed gene content and expression in the nuclear genome of the psyllid Pachypsylla venusta, a sap-feeding insect that harbors an ancient endosymbiont (Carsonella) with one of the most reduced bacterial genomes ever identified. Carsonella retains many genes required for synthesis of essential amino acids that are scarce in plant sap, but most of these biosynthetic pathways have been disrupted by gene loss. Host genes that are upregulated in psyllid cells housing Carsonella appear to compensate for endosymbiont gene losses, resulting in highly integrated metabolic pathways that mirror those observed in other sap-feeding insects. The host contribution to these pathways is mediated by a combination of native eukaryotic genes and bacterial genes that were horizontally transferred from multiple donor lineages early in the evolution of psyllids, including one gene that appears to have been directly acquired from Carsonella. By comparing the psyllid genome to a recent analysis of mealybugs, we found that a remarkably similar set of functional pathways have been shaped by independent transfers of bacterial genes to the two hosts. These results show that horizontal gene transfer is an important and recurring mechanism driving coevolution between insects and their bacterial endosymbionts and highlight interesting similarities and contrasts with the evolutionary history of mitochondria and plastids.
Factors Associated With Receipt of Breast Cancer Adjuvant Chemotherapy in a Diverse Population-Based Sample
Authors: Jennifer J. Griggs, Sarah T. Hawley, John J. Graff, Ann S. Hamilton, Reshma Jagsi, Nancy K. Janz, Mahasin S. Mujahid, Christopher R. Friese, Barbara Salem, Paul H. Abrahamse, Steven J. Katz
Journal: Journal of Clinical Oncology (2012)

Disparities in receipt of adjuvant chemotherapy may contribute to higher breast cancer fatality rates among black and Hispanic women compared with non-Hispanic whites. We investigated factors associated with receipt of chemotherapy in a diverse population-based sample.Women diagnosed with breast cancer between August 2005 and May 2007 (N = 3,252) and reported to the Detroit, Michigan, or Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registry were recruited to complete a survey. Multivariable analyses examined factors associated with chemotherapy receipt.The survey was sent to 3,133 patients; 2,290 completed a survey (73.1%), and 1,403 of these patients were included in the analytic sample. In multivariable models, disease characteristics were significantly associated with the likelihood of receiving chemotherapy. Low-acculturated Hispanics were more likely to receive chemotherapy than non-Hispanic whites (odds ratio [OR], 2.00; 95% CI, 1.31 to 3.04), as were high-acculturated Hispanics (OR, 1.43; 95% CI, 1.03 to 1.98). Black women were less likely to receive chemotherapy than non-Hispanic whites, but the difference was not significant (OR, 0.83; 95% CI, 0.64 to 1.08). Increasing age (even in women age < 50 years) and Medicaid insurance were associated with lower rates of chemotherapy receipt.In this population-based sample, disease characteristics were strongly associated with receipt of chemotherapy, indicating that clinical benefit guides most treatment decisions. We found no compelling evidence that black women and Hispanics receive chemotherapy at lower rates. Interventions that address chemotherapy use rates according to age and insurance status may improve quality of systemic treatment.
Reversible Pancytopenia Caused by Oral Letrozole Assumption in a Patient With Recurrent Breast Cancer
Authors: Paola Sperone, Gabriella Gorzegno, Alfredo Berruti, Ubaldo Familiari, Luigi Dogliotti
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.99.138 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12202678 Reversible Pancytopenia Caused by Oral Letrozole Assumption in a Patient With Recurrent Breast Cancer Paola SperonexPaola SperoneSearch for articles by this author , Gabriella GorzegnoxGabriella GorzegnoSearch for articles by this author , Alfredo BerrutixAlfredo BerrutiSearch for articles by this author , Ubaldo FamiliarixUbaldo FamiliariSearch for articles by this author , Luigi DogliottixLuigi DogliottiSearch for articles by this author Show More Università di Torino, Oncologia Medica, Anatomia Patologica, Azienda Ospedaliera San Luigi, Polo Oncologico di Orbassano, Orbassano, Italy https://doi.org/10.1200/JCO.2002.99.138 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Total Systemic Vascular Compliance Measured as Incremental Volume-Pressure Ratio
Authors: ARTIN A. SHOUKAS, KIICHI SAGAWA
Journal: Circulation Research (1971)

We developed a method to measure the compliance, defined as ΔVΔP, of the total systemic vascular bed (C t ) without stopping systemic flow. In 10 open-chest dogs, venous return (and cardiac output) was maintained at a constant level by inserting a perfusion pump (with no reservoir) between the caval veins and the right atrium. About 5% of the estimated total blood volume was withdrawn from the dog within 45 seconds. Resultant changes in central venous pressure were measured 10, 30, 60, 120, and 180 seconds after the volume change. The bled volume was then reinfused to repeat similar venous pressure measurements for another 180 seconds. The measurements were repeated after slightly increasing the blood volume or sectioning the vagi. The mean value of C t measured 10 seconds after hemorrhage or reinfusion was 1.96 ± 0.10 ( SE ) ml/mm Hg/kg body weight before vagotomy. Paired t -tests indicated no significant difference between measurements of bleeding and reinfusion, measurements with different initial venous pressures or blood volume, or measurements before and after vagotomy. However, C t increased with time during the 2-minute period by about 25% of the initial 10-second value ( P &lt;0.001) and remained constant thereafter.
Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study
Authors: Giuseppe Realdi, Giovanna Fattovich, Stephanos Hadziyannis, Solko W. Schalm, Piero Almasio, Josè Sanchez-Tapias, Erik Christensen, Giuliano Giustina, Franco Noventa
Journal: Journal of Hepatology (1994)
Lung toxicity in a patient treated with sunitinib
Authors: Helen J. Boyle, Gérard Chatté, Michel Rivoire, Aude Fléchon
Journal: European Respiratory Journal (2012)

for the effusion, which led to the diagnosis of pancreaticopleural fistula with histology confirming that it arose from a pancreatic intraductal papillary mucinous neoplasm.Our patient remains well and at most recent follow-up, .18months post-surgery, the effusion has not recurred.
Gefitinib or Placebo in Combination with Tamoxifen in Patients with Hormone Receptor–Positive Metastatic Breast Cancer: A Randomized Phase II Study
Authors: C. Kent Osborne, Patrick Neven, Luc Y. Dirix, John R. Mackey, Jean Robert, Craig Underhill, Rachel Schiff, Carolina Gutierrez, Ilenia Migliaccio, Valsamo K. Anagnostou, David L. Rimm, Patrick Magill, Mark Sellers
Journal: Clinical Cancer Research (2011)

Increased growth factor signaling may contribute to tamoxifen resistance. This randomized phase II trial assessed tamoxifen plus placebo or the epidermal growth factor receptor inhibitor gefitinib in estrogen receptor (ER)-positive metastatic breast cancer.Patients with newly metastatic disease or recurred after adjuvant tamoxifen (stratum 1), or recurred during/after adjuvant aromatase inhibitor (AI) or after failed first-line AI (stratum 2), were eligible. Primary variables were progression-free survival (PFS; stratum 1) and clinical benefit rate (CBR; stratum 2). A 5% or more improvement in response variables with gefitinib was considered to warrant further investigation. Outcome was correlated with biomarkers measured on the primary tumor.In stratum 1 (n = 206), the PFS HR (gefitinib:placebo) was 0.84 (95% CI, 0.59-1.18; median PFS 10.9 versus 8.8 months). In the stratum 1 endocrine therapy-naïve subset (n = 158) the HR was 0.78 (95% CI, 0.52-1.15), and the prior endocrine-treated subgroup (n = 48) 1.47 (95% CI, 0.63-3.45). In stratum 1, CBRs were 50.5% with gefitinib and 45.5% with placebo. In stratum 2 (n = 84), CBRs were 29.2% with gefitinib and 31.4% with placebo. Biomarker analysis suggested that in stratum 1 there was greater benefit with gefitinib in patients who were ER-negative or had lower levels of ER protein.In stratum 1, the improved PFS with gefitinib plus tamoxifen met the protocol criteria to warrant further investigation of this strategy. In stratum 2, there was a numerical disadvantage for gefitinib; additional investigation after AI therapy is not warranted. Studies of predictive biomarkers are needed to subset appropriate patients.
Reduced Incidence of Lower-Limb Amputations in the Diabetic Population of a German City, 1990–2005
Authors: Christoph Trautner, Burkhard Haastert, Peter Mauckner, Lena-Maria Gätcke, Guido Giani
Journal: Diabetes Care (2007)

We evaluated whether the incidence of amputations in one German city (Leverkusen, population approximately 160,000) had decreased between 1990 and 2005.From all three hospitals in the city, we obtained complete lists of nontraumatic lower-limb amputations in 1990-1991 and 1994-2005. Only the first observed amputation in residents of Leverkusen was counted. A total of 692 patients met the inclusion criteria. Data about the population structure, separately for each year of the observation period, were received from the city administration and the Federal Office of Statistics. To test for time trend, we fitted Poisson regression models.Of all subjects, 72% had known diabetes and 58% were male. Mean age was 71.7 years. Incidence rates in the diabetic population (standardized to the estimated German diabetic population per 100,000 person-years) varied considerably between years (maximum 549 in 1990, minimum 281 in 2004). In the diabetic population, the estimated relative risk (RR) per year was 0.976 (95% CI 0.958-0.996, P = 0.0164). The same trend was observed when only amputations above the ankle (n = 352) (RR 0.970 [95% CI 0.943-0.997], P = 0.0318) were considered. Over 15 years, an estimated reduction of amputations above the toe level by 37.1% (95% CI 12.3-54.8) results. There was no significant change of incident amputations in the nondiabetic population (RR 1.022 [0.989-1.056], P = 0.1981).This finding is likely to be due to improved management of the diabetic foot syndrome after a network of specialized physicians and defined clinical pathways for wound treatment and metabolic control were introduced.
Nitrates and Glaucoma
Authors: David Robertson
Journal: JAMA (1977)

<h3>To the Editor.—</h3> We felt Dr Reichek's recent review "Long-Acting Nitrates in the Treatment of Angina Pectoris" (236:1399, 1976) was an excellent survey of the clinical pharmacology of these compounds. However, he raised one point with which we cannot fully agree and which we feel the recent literature does not support. In the discussion on toxicity of the nitrates, Dr Reichek states, "Nitrates raise intraocular pressure and are relatively contraindicated in patients with glaucoma." This assertion is probably based on similar statements in a number of older textbooks of pharmacology, which themselves are based on rather tenuous experiments performed many years ago. These suggested that intraocular pressure could occasionally be raised slightly for a short period of time by amyl nitrite inhalation. Over a period of years, this limited and inconsistent finding was extrapolated into a pharmacological legend that was perpetuated in textbooks and the manufacturers' literature. The history of
Early hepatitis B virus DNA reduction in hepatitis B e antigen-positive patients with chronic hepatitis B: A randomized international study of entecavir versus adefovir
Authors: Nancy Leung, Cheng‐Yuan Peng, Hie‐Won Hann, Jose Sollano, Judy Lao‐Tan, Chao‐Wei Hsu, Laurentius Lesmana, Man‐Fung Yuen, Lennox Jeffers, Morris Sherman, Albert Min, Kimberly Mencarini, Ulysses Diva, Anne Cross, Richard Wilber, Juan Lopez‐Talavera
Journal: Hepatology (2008)

This study was undertaken to compare the early antiviral activity and viral kinetic profiles of entecavir (ETV) versus adefovir (ADV) in hepatitis B e antigen positive nucleoside-naïve adults with chronic hepatitis B (CHB). Sixty-nine nucleoside-naïve CHB patients with baseline HBV DNA of 10(8) copies/mL or more were randomized 1:1 to open-label treatment with entecavir 0.5 mg/day or adefovir 10 mg/day for a minimum of 52 weeks. The primary efficacy analysis compared mean reduction in HBV DNA at week 12 adjusted for baseline levels using linear regression. Entecavir was superior to adefovir for mean change from baseline in HBV DNA at week 12 (-6.23 log(10) copies/mL versus -4.42 log(10) copies/mL, respectively; mean difference -1.58 log(10) copies/mL; P < 0.0001). Both drugs demonstrated biphasic viral kinetics, with a first phase of rapid decline lasting 10 days. A significant difference favoring ETV was reached at day 10 (day 10 ETV-ADV difference estimate: -0.66 log(10) copies/mL; 95% CI [-0.30, -0.01]). Early virological response was found to be predictive of subsequent virological response, with those having lower HBV DNA levels at day 10 being more likely to achieve HBV DNA of less than 300 copies/mL at week 48. In addition, there was considerably less variability in the extent of HBV DNA reductions in patients treated with entecavir versus adefovir. Both the mean decrease in serum HBV DNA and the proportion of patients achieving HBV DNA less than 300 copies/mL were greater in entecavir-treated than adefovir-treated patients at weeks 2, 4, 8, 12, 24, and 48. At week 48, one (3%) ETV-treated versus 15 (47%) ADV-treated patients had HBV DNA of 10(5) copies/mL or more. Both antivirals were well tolerated.Entecavir therapy resulted in earlier and superior reduction in HBV DNA compared with adefovir in nucleoside-naïve HBeAg-positive patients with CHB.
Aspergillus fumigatus conidia induce interferon- signalling in respiratory epithelial cells
Authors: C. Beisswenger, C. Hess, R. Bals
Journal: European Respiratory Journal (2011)

Aspergillus fumigatus is a fungal pathogen of major clinical importance. However, little is known about the role of human bronchial epithelial cells (HBECs) during A. fumigatus conidia induced inflammation. Here, we show that differentiated respiratory epithelial cells recognise inactivated resting conidia but not swollen conidia or hyphae, resulting in the induction of the interferon (IFN)-β signalling pathway and the expression of IFN-β-inducible genes, such as IFN-γ-inducible protein (IP)-10. This induction was internalisation dependent. We identified double-stranded conidial RNA recognised by Toll-like receptor-3 as a factor responsible for the expression of IFN-β and IP-10. Inhibition of receptor-interacting protein-1/TANK-binding kinase-1, known to mediate IFN-β signalling, was sufficient to inhibit the induction of IFN-β and IP-10 expression by conidia. Even though conidia induced the activation of nuclear factor (NF)-κB in HBECs, IP-10 expression was only partially dependent on NF-κB signalling. These results provide evidence that respiratory cells are activated by the double-stranded RNA of resting conidia and initiate a first immune response to inhaled conidia in an IFN-β-dependent manner.
Strategies for Cadaveric Organ Procurement
Authors: John Glasson
Journal: JAMA (1994)

<h3>THE SCARCITY OF ORGANS FOR TRANSPLANTATION</h3> The shortage of organs for transplantation is becoming more critical every year. Because of improvements in transplantation procedures, beginning with the advent of immunosuppressive therapies in the early 1980s, more patients now benefit from organ transplantation. As a result of transplantation's success, waiting lists for donor organs are increasingly crowded. Between December 1987 and June 1991, for example, the total number of patients on organ transplant waiting lists increased 75.3%, from 13153 to 23 056 patients.<sup>1</sup> For editorial comment see p 814. Tragically, the supply of donated organs has not kept up with this demand. Between 1987 and 1990, the number of organ donors per year stayed nearly constant, increasing from 4000 to 4357.<sup>1</sup>Even though each cadaveric organ donor can often supply multiple organs for transplantation, many patients still die before a suitable organ becomes available. In September 1991, the United