tbuckley/cabot-search huggingface dataset:
Unmasked tuberculosis or lymphoma in late AIDS presenters: a difficult differential diagnosis
Authors: A. Soria, S. Foresti, P. Fortuna, A. Dolara, A. Bandera, G. Lapadula, A. Gori
Journal: European Respiratory Journal (2009)

To the Editors :

Despite dramatic progress in the management of HIV infection 1, late presentation remains a major threat to survival 2. Difficult diagnosis of AIDS-related illnesses could pose additional challenge. Tuberculosis (TB) is considered to be the most frequent opportunistic infection worldwide. Smear-negative pulmonary TB or extrapulmonary TB diagnosis may be difficult to rule out, either because of inadequate laboratory markers, or overlapping clinical presentation with other conditions, such as lymphoproliferative disorders. In addition, in the era of combination antiretroviral therapy (cART), unmasked TB could develop as immune reconstitution inflammatory syndrome (IRIS) after cART is commenced in treatment-naive subjects with advanced HIV infection. Here we describe two cases of AIDS-related diseases, with similar presentation but different diagnosis and outcome.

The first patient was a 37-yr-old male, who was born in Togo and had lived in Italy for 2 yrs, presented to our attention in May 2008 for mild fever and chest pain. He had been diagnosed for the first time with pulmonary TB (acid-fast bacilli in the sputum smear) and advanced HIV infection (CD4+ T-cell count 40 cells·mm−3) 2 months earlier, elsewhere. The patient had been treated for 2 months with rifampin, isoniazid, ethambutol and pyrazinamide, but had not started cART. On admission, physical examination showed enlargement of the liver, but no superficial lymphadenopathy. Laboratory tests showed mild anaemia (haemoglobin 11.7 g·dL−1, mean corpuscolar volume 75.9 fL), normal white blood cells and platelet count, and increased erythrocyte sedimentation rate (72 mm·h−1) and levels of serum lactate dehydrogenase (LDH) (1,173 IU·L−1). Chest radiography revealed bilateral perihilar and lower right lung …
Combined effects of obesity, acid reflux and smoking on the risk of adenocarcinomas of the oesophagus
Authors: D C Whiteman, S Sadeghi, N Pandeya, B M Smithers, D C Gotley, C J Bain, P M Webb, A C Green
Journal: Gut (2007)

To measure the relative risks of adenocarcinomas of the oesophagus and gastro-oesophageal junction associated with measures of obesity, and their interactions with age, sex, gastro-oesophageal reflux symptoms and smoking.Population-based case-control study in Australia.Patients with adenocarcinomas of the oesophagus (n = 367) or gastro-oesophageal junction (n = 426) were compared with control participants (n = 1580) sampled from a population register.Relative risk of adenocarcinoma of the oesophagus or gastro-oesophageal junction.Risks of oesophageal adenocarcinoma increased monotonically with body mass index (BMI) (p(trend) <0.001). Highest risks were seen for BMI >or=40 kg/m2 (odds ratio (OR) = 6.1, 95% CI 2.7 to 13.6) compared with "healthy" BMI (18.5-24.9 kg/m2). Adjustment for gastro-oesophageal reflux and other factors modestly attenuated risks. Risks associated with obesity were substantially higher among men (OR = 2.6, 95% CI 1.8 to 3.9) than women (OR = 1.4, 95% CI 0.5 to 3.5), and among those aged <50 years (OR = 7.5, 95% CI 1.7 to 33.0) than those aged >or=50 years (OR = 2.2, 95% CI 1.5 to 3.1). Obese people with frequent symptoms of gastro-oesophageal reflux had significantly higher risks (OR = 16.5, 95% CI 8.9 to 30.6) than people with obesity but no reflux (OR = 2.2, 95% CI 1.1 to 4.3) or reflux but no obesity (OR = 5.6, 95% 2.8 to 11.3), consistent with a synergistic interaction between these factors. Similar associations, but of smaller magnitude, were seen for gastro-oesophageal junction adenocarcinomas.Obesity increases the risk of oesophageal adenocarcinoma independently of other factors, particularly among men. From a clinical perspective, these data suggest that patients with obesity and frequent symptoms of gastro-oesophageal reflux are at especially increased risk of adenocarcinoma.
Involvement of a Postsynaptic Protein Kinase A Substrate in the Expression of Homosynaptic Long-Term Depression
Authors: Kimihiko Kameyama, Hey-Kyoung Lee, Mark F Bear, Richard L Huganir
Journal: Neuron (1998)

Hippocampal N-methyl-D-aspartate (NMDA) receptor-dependent long-term synaptic depression (LTD) is associated with a persistent dephosphorylation of the GluR1 subunit of AMPA receptors at a site (Ser-845) phosphorylated by cAMP-dependent protein kinase (PKA). In the present study, we show that dephosphorylation of a postsynaptic PKA substrate may be crucial for LTD expression. PKA activators inhibited both AMPA receptor dephosphorylation and LTD. Injection of a cAMP analog into postsynaptic neurons prevented LTD induction and reversed previously established homosynaptic LTD without affecting baseline synaptic transmission. Moreover, infusing a PKA inhibitor into postsynaptic cells produced synaptic depression that occluded homosynaptic LTD. These findings suggest that dephosphorylation of a PKA site on AMPA receptors may be one mechanism for NMDA receptor-dependent homosynaptic LTD expression.
The Exocytosis-Regulatory Protein Synaptotagmin VII Mediates Cell Invasion by <i>Trypanosoma cruzi</i>
Authors: Elisabet V. Caler, Sabyasachi Chakrabarti, Kimberly T. Fowler, Swathi Rao, Norma W. Andrews
Journal: The Journal of Experimental Medicine (2001)

The intracellular protozoan parasite Trypanosoma cruzi causes Chagas' disease, which affects millions of people in Latin America. T. cruzi enters a large number of cell types by an unusual mechanism that involves Ca2+-triggered fusion of lysosomes with the plasma membrane. Here we show that synaptotagmin VII (Syt VII), a ubiquitously expressed synaptotagmin isoform that regulates exocytosis of lysosomes, is localized on the membranes of intracellular vacuoles containing T. cruzi. Antibodies against the C2A domain of Syt VII or recombinant peptides including this domain inhibit cell entry by T. cruzi, but not by Toxoplasma gondii or Salmonella typhimurium. The C2A domains of other ubiquitously expressed synaptotagmin isoforms have no effect on T. cruzi invasion, and mutation of critical residues on Syt VII C2A abolish its inhibitory activity. These findings indicate that T. cruzi exploits the Syt VII–dependent, Ca2+-regulated lysosomal exocytic pathway for invading host cells.
Dose response relationships of insulin hypoglycaemia and gastric acid in man
Authors: J. H. Baron
Journal: Gut (1970)

Fourteen studies of gastric acid secretion in a basal hour and in the two hours after a single intravenous injection of soluble insulin (0·01 to 0·40 units/kg) were performed in a healthy man. The peak acid output after insulin (measured as the two consecutive 15-minute samples giving the highest acid output) was significantly correlated with the lowest concentration of blood glucose, the fall in blood glucose, the rate of fall of blood glucose, and the maximum fall of blood glucose in any 15 minutes. Peak acid outputs after insulin were similar over the range 0·1 to 0·2 units/kg, and greater than at lower or higher doses. These results are contrary to the accepted assumption that insulin-stimulated acid secretion is an `all-or-none9 phenomenon. They support instead the hypothesis that insulin hypoglycaemia provides a quantitative glycopenic stimulus producing quantitative vagal acid response. Extreme hypoglycaemia, below about 15 mg/100 ml of blood glucose, inhibits insulin-stimulated acid secretion.
Obstetric Risk Factors for Early-Onset Schizophrenia in a Finnish Birth Cohort
Authors: Isabelle M. Rosso, Tyrone D. Cannon, Tiia Huttunen, Matti O. Huttunen, Jouko Lï¿½vist, Timothy L. Gasperoni
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Although case-control investigations have shown an association between obstetric complications and schizophrenia, particularly among patients with early onsets, cohort studies have mostly failed to confirm this effect. The authors examined whether a history of fetal hypoxia and other obstetric complications elevated risk for early-onset schizophrenia in a 1955 Helsinki birth cohort. METHOD: The subjects were 80 randomly selected patients with schizophrenia (36 with early and 44 with later onsets) representative of all available probands in the cohort, 61 of their nonschizophrenic siblings, and 56 demographically matched nonpsychiatric comparison subjects. Psychiatric diagnoses were obtained from structured clinical interviews, and obstetric data were taken from standardized, prospectively ascertained obstetric records. A score for hypoxia-associated obstetric complications was entered into logistic regression models, along with measures of prenatal infection and fetal growth retardation. RESULTS: Hypoxia-associated obstetric complications significantly increased the odds of early-onset schizophrenia but not of later-onset schizophrenia or unaffected sibling status, after prenatal infection and fetal growth retardation were taken into account. CONCLUSIONS: These findings support an association between obstetric complications and increased risk for early-onset schizophrenia. The authors advance a model whereby the neurotoxic effects of fetal hypoxia may lead to an early onset of schizophrenia due to premature cortical synaptic pruning.
ERS guidelines on the assessment of cough
Authors: A. H. Morice, G. A. Fontana, M. G. Belvisi, S. S. Birring, K. F. Chung, P. V. Dicpinigaitis, J. A. Kastelik, L. P. McGarvey, J. A. Smith, M. Tatar, J. Widdicombe
Journal: European Respiratory Journal (2007)

Cough 1) All basic scientific articles should refer to cough as a three-phase motor act.For the purposes of acoustic recordings in clinical studies, however, cough should be described as a forced expulsive manoeuvre or manoeuvres against a closed glottis that are associated with a characteristic sound or sounds.
Lean mass predicts asthma better than fat mass among females
Authors: A. Sood, C. Qualls, R. Li, M. Schuyler, W.S. Beckett, L.J. Smith, B. Thyagarajan, C.E. Lewis, D.R. Jacobs
Journal: European Respiratory Journal (2010)

The obesity phenotype associated with asthma is not known. Our objective was to define the relative contribution of various distributions of fat and lean mass to asthma prevalence. Data were obtained from 2,525 participants (including 1,422 females) who underwent dual-energy X-ray absorptiometry (DEXA) at the year 20 examination in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Total, truncal, arm and leg distributions of fat and lean mass were adjusted to the person's height. Self-reported asthma was the outcome. Asthma among females was associated with greater total fat mass, arm fat mass, total lean mass, truncal lean mass and arm lean mass. Among males, none of these mass measures were significantly associated with asthma. Among females, the association with asthma was stronger for total lean mass than for total fat mass. Further, among various regional distributions of lean and fat mass in females, truncal lean mass was the strongest predictor. Total lean mass is more strongly associated with asthma than total fat mass among females. These findings are contrary to the popular perception that excess physiological fat drives the obesity-asthma association. Rather, we hypothesise that ectopic fat within the "lean" tissues drives this association among females.
Dyslipidemia inhibits Toll-like receptor–induced activation of CD8α-negative dendritic cells and protective Th1 type immunity
Authors: Abdijapar T. Shamshiev, Franziska Ampenberger, Bettina Ernst, Lucia Rohrer, Benjamin J. Marsland, Manfred Kopf
Journal: The Journal of Experimental Medicine (2007)

Environmental factors, including diet, play a central role in influencing the balance of normal immune homeostasis; however, many of the cellular mechanisms maintaining this balance remain to be elucidated. Using mouse models of genetic and high-fat/cholesterol diet–induced dyslipidemia, we examined the influence of dyslipidemia on T cell and dendritic cell (DC) responses in vivo and in vitro. We show that dyslipidemia inhibited Toll-like receptor (TLR)–induced production of proinflammatory cytokines, including interleukin (IL)-12, IL-6, and tumor necrosis factor-α, as well as up-regulation of costimulatory molecules by CD8α− DCs, but not by CD8α+ DCs, in vivo. Decreased DC activation profoundly influenced T helper (Th) cell responses, leading to impaired Th1 and enhanced Th2 responses. As a consequence of this immune modulation, host resistance to Leishmania major was compromised. We found that oxidized low-density lipoprotein (oxLDL) was the key active component responsible for this effect, as it could directly uncouple TLR-mediated signaling on CD8α− myeloid DCs and inhibit NF-κB nuclear translocation. These results show that a dyslipidemic microenvironment can directly interfere with DC responses to pathogen-derived signals and skew the development of T cell–mediated immunity.
Enzalutamide for Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer Who Have Previously Received Docetaxel: U.S. Food and Drug Administration Drug Approval Summary
Authors: Yangmin M. Ning, William Pierce, V. Ellen Maher, Stella Karuri, Sheng-Hui Tang, Haw-Jyh Chiu, Todd Palmby, Jeanne Fourie Zirkelbach, Dhananjay Marathe, Nitin Mehrotra, Qi Liu, Debasis Ghosh, Christy L. Cottrell, John Leighton, Rajeshwari Sridhara, Amna Ibrahim, Robert Justice, Richard Pazdur
Journal: Clinical Cancer Research (2013)

Abstract This article summarizes the regulatory evaluation that led to the full approval of enzalutamide (XTANDI, Medivation Inc.) by the U.S. Food and Drug Administration (FDA) on August 31, 2012, for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. This approval was based on the results of a randomized, placebo-controlled trial which randomly allocated 1,199 patients with mCRPC who had received prior docetaxel to receive either enzalutamide, 160 mg orally once daily (n = 800), or placebo (n = 399). All patients were required to continue androgen deprivation therapy. The primary endpoint was overall survival. At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for the enzalutamide arm compared with the placebo arm [HR = 0.63; 95% confidence interval: 0.53–0.75; P &amp;lt; 0.0001]. The median overall survival durations were 18.4 months and 13.6 months in the enzalutamide and placebo arms, respectively. The most common adverse reactions (≥10%) included asthenia or fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, and upper respiratory infection. Seizures occurred in 0.9% of patients on enzalutamide compared with no patients on the placebo arm. Overall, the FDA's review and analyses of the submitted data confirmed that enzalutamide had a favorable benefit–risk profile in the study patient population, thus supporting its use for the approved indication. The recommended dose is 160 mg of enzalutamide administered orally once daily. Enzalutamide represents the third product that the FDA has approved in the same disease setting within a period of 2 years. Clin Cancer Res; 19(22); 6067–73. ©2013 AACR.
Elevated serum osteopontin level is associated with blood eosinophilia and asthma comorbidity in patients with allergic rhinitis
Authors: Wenlong Liu, Wentong Xia, Yunping Fan, Hongtian Wang, Kejun Zuo, Yinyan Lai, Huabin Li, Zheng Liu, Jianbo Shi, Geng Xu
Journal: Journal of Allergy and Clinical Immunology (2012)
A Trans-Specific Polymorphism in ZC3HAV1 Is Maintained by Long-Standing Balancing Selection and May Confer Susceptibility to Multiple Sclerosis
Authors: R. Cagliani, F. R. Guerini, M. Fumagalli, S. Riva, C. Agliardi, D. Galimberti, U. Pozzoli, A. Goris, B. Dubois, C. Fenoglio, D. Forni, S. Sanna, I. Zara, M. Pitzalis, M. Zoledziewska, F. Cucca, F. Marini, G. P. Comi, E. Scarpini, N. Bresolin, M. Clerici, M. Sironi
Journal: Molecular Biology and Evolution (2012)

The human ZC3HAV1 gene encodes an antiviral protein. The longest splicing isoform of ZC3HAV1 contains a C-terminal PARP-like domain, which has evolved under positive selection in primates. We analyzed the evolutionary history of this same domain in humans and in Pan troglodytes. We identified two variants that segregate in both humans and chimpanzees; one of them (rs3735007) does not occur at a hypermutable site and accounts for a nonsynonymous substitution (Thr851Ile). The probability that the two trans-specific polymorphisms have occurred independently in the two lineages was estimated to be low (P = 0.0054), suggesting that at least one of them has arisen before speciation and has been maintained by selection. Population genetic analyses in humans indicated that the region surrounding the shared variants displays strong evidences of long-standing balancing selection. Selection signatures were also observed in a chimpanzee population sample. Inspection of 1000 Genomes data confirmed these findings but indicated that search for selection signatures using low-coverage whole-genome data may need masking of repetitive sequences. A case–control study of more than 1,000 individuals from mainland Italy indicated that the Thr851Ile SNP is significantly associated with susceptibility to multiple sclerosis (MS) (odds ratio [OR] = 1.47, 95% confidence intervals [CI]: 1.08–1.99, P = 0.011). This finding was confirmed in a larger sample of 4,416 Sardinians cases/controls (OR = 1.18, 95% CI: 1.037–1.344, P = 0.011), but not in a population from Belgium. We provide one of the first instances of human/chimpanzee trans-specific coding variant located outside the major histocompatibility complex region. The selective pressure is likely to be virus driven; in modern populations, this variant associates with susceptibility to MS, possibly via the interaction with environmental factors.
The presence of forefoot problems and the role of surgery in patients with rheumatoid arthritis
Authors: G A Matricali, A Boonen, J Verduyckt, V Taelman, P Verschueren, A Sileghem, L Corluy, R Westhovens
Journal: Annals of the Rheumatic Diseases (2006)

Foot problems constitute a major problem in up to 90% of patients with rheumatoid arthritis, causing pain and functional limitations.1,2 Forefoot deformities are often complicated by ulcers, which can infect the foot and result in major septic complications. Although no data are available on the effect of foot problems on function and quality of life in patients with rheumatoid arthritis, in patients with diabetes mellitus these scores drop substantially.3

Foot problems can be treated by the use of orthotic devices and custom-made shoes, or by a variety of surgical techniques.1,4 We conducted a cross-sectional, multicentre study to assess the burden of forefoot problems and current management in 285 consecutive patients with rheumatoid arthritis in five university and non-university centres between January and April 2004. The mean age of patients was 57 years …
THE INFLUENCE OF NITROGEN RETENTION UPON THE REGENERATION OF PLASMA PROTEINS
Authors: Russell L. Holman, J. Gilmer Mebane
Journal: The Journal of Experimental Medicine (1940)

1. Because of the clinical observation that the capacity to form new plasma proteins is sometimes impaired in cases of nephritis (2), experiments were performed to determine whether the impaired function in the nephritic is related to nitrogen retention. 2. These experiments consisted of producing renal injury by injecting uranium nitrate into standard hypoproteinemic dogs and comparing the rate of blood plasma protein formation under these conditions of nitrogen retention with that in the uninjured dog. 3. Despite elevations in blood N.P.N. to more than ten times normal, no interference with plasma protein formation was observed. These elevations in N.P.N. affected principally the urea and undetermined fractions. 4. Neither elevation in N.P.N. nor proteinuria per se appears to have any effect upon plasma protein production. Possibly the deficient production of plasma proteins in the nephritic is related to a more general disturbance in metabolism in which the elevation in N.P.N. is secondary.
Preservation of aortic root architecture and properties using a detergent-enzymatic perfusion protocol
Authors: Linda H. Friedrich, Philipp Jungebluth, Sebastian Sjöqvist, Vanessa Lundin, Johannes C. Haag, Greg Lemon, Ylva Gustafsson, Fatemeh Ajalloueian, Alexander Sotnichenko, Heike Kielstein, Miguel A. Burguillos, Bertrand Joseph, Ana I. Teixeira, Mei Ling Lim, Paolo Macchiarini
Journal: Biomaterials (2013)
SPECIFICITY IN THE EFFECTS ON BRAIN METABOLISM OF TWO DIFFERING NEUROTROPIC VIRUSES
Authors: Margaret Nickle, Herman Kabat
Journal: The Journal of Experimental Medicine (1944)

1. Brain tissue infected with the virus of Western equine encephalomyelitis shows specific differences in metabolism from brain tissue infected with the virus of poliomyelitis. 2. With added glucose concentration of 121 mg. per cent, oxygen utilization of poliomyelitic brain is significantly below normal and that of encephalitic brain is not. 3. With added glucose concentration of 217 mg. per cent, oxygen utilization of encephalitic brain is significantly below normal and that of poliomyelitic brain is not. 4. With lactate-glucose as the substrate, oxygen utilization of encephalitic brain is significantly below normal and that of poliomyelitic brain is not. 5. With pyruvate-glucose as the substrate, neither encephalitic brain nor poliomyelitic brain differs significantly from normal in oxygen consumption. 6. With succinate-glucose as the substrate, oxygen utilization of poliomyelitic brain is significantly above that of the normal control in the 1st hour. 7. With added glucose concentration of 37.5 mg. per cent, anaerobic metabolism of encephalitic brain is significantly below the normal whereas that of poliomyelitic brain is not. 8. With added glucose concentration of 229.5 mg. per cent, anaerobic metabolism of both encephalitic brain and poliomyelitic brain is significantly below the normal.
Estradiol and Bisphenol A Stimulate Androgen Receptor and Estrogen Receptor Gene Expression in Fetal Mouse Prostate Mesenchyme Cells
Authors: Catherine A. Richter, Julia A. Taylor, Rachel L. Ruhlen, Wade V. Welshons, Frederick S. vom Saal
Journal: Environmental Health Perspectives (2007)

Hormonal alterations during development have lifelong effects on the prostate gland. Endogenous estrogens, including 17beta-estradiol (E(2)), and synthetic estrogenic endocrine disruptors, such as bisphenol A (BPA), have similar effects on prostate development. Increasing exposure to estrogens within the low-dose, physiologic range results in permanent increases in the size and androgen responsiveness of the prostate, whereas exposure within the high-dose, pharmacologic range has the opposite effects.We tested the hypothesis that the low-dose effects of estrogens on the developing prostate are associated with increased expression of androgen receptor (Ar) and estrogen receptor 1 (alpha) (Esr1) genes in mesenchyme cells.Ar and Esr1 mRNA levels were quantified in primary cultures of fetal mouse prostate mesenchyme cells treated with E(2) and BPA.Ar and Esr1 mRNA expression increased in response to E(2), with thresholds of 0.001 and 0.037 nM, respectively; and in response to BPA, with a threshold of 1 nM for both mRNAs. We did not observe the expected inhibition of Ar mRNA expression by pharmacologic levels of E(2) relative to unexposed cells.The observed induction of gene expression occurred at concentrations within the range of free E(2) previously shown to permanently increase prostate size, thus supporting the involvement of direct effects of estrogens on gene expression in prostate mesenchyme. The effects of BPA occurred within the range of concentrations currently measured in human serum, demonstrating the vulnerability of developing tissues to xenoestrogens.