tbuckley/cabot-search huggingface dataset:
Allergenic pollen and pollen allergy in Europe
Authors: G. D’Amato, L. Cecchi, S. Bonini, C. Nunes, I. Annesi‐Maesano, H. Behrendt, G. Liccardi, T. Popov, P. Van Cauwenberge
Journal: Allergy (2007)

The allergenic content of the atmosphere varies according to climate, geography and vegetation. Data on the presence and prevalence of allergenic airborne pollens, obtained from both aerobiological studies and allergological investigations, make it possible to design pollen calendars with the approximate flowering period of the plants in the sampling area. In this way, even though pollen production and dispersal from year to year depend on the patterns of preseason weather and on the conditions prevailing at the time of anthesis, it is usually possible to forecast the chances of encountering high atmospheric allergenic pollen concentrations in different areas. Aerobiological and allergological studies show that the pollen map of Europe is changing also as a result of cultural factors (for example, importation of plants such as birch and cypress for urban parklands), greater international travel (e.g. colonization by ragweed in France, northern Italy, Austria, Hungary etc.) and climate change. In this regard, the higher frequency of weather extremes, like thunderstorms, and increasing episodes of long range transport of allergenic pollen represent new challenges for researchers. Furthermore, in the last few years, experimental data on pollen and subpollen-particles structure, the pathogenetic role of pollen and the interaction between pollen and air pollutants, gave new insights into the mechanisms of respiratory allergic diseases.
S40 A comparison of asthmatic and non-asthmatic severe small airway disease
Authors: DJ Wilkinson, HGT Brice, L Holmes, SJ Fowler, R Niven
Journal: Thorax (2013)

<h3>Introduction</h3> We present a series of cases referred to our severe asthma clinic that symptomatically appear like asthma, yet physiology demonstrated one of the more uncommon types of severe Small Airway Disease (SAD), including: Allergic Bronchopulmonary Aspergillosis (ABPA), Obliterative Bronchiolitis (OB), follicular bronchiolitis and Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH). These diseases represent a diagnostic challenge. We have also reviewed cases of tracheomalacia and horseshoe lung, which in our report shared similar physiology to SAD. <h3>Methods</h3> Our findings in these SAD patients are compared with randomly identified cases of genuine severe asthma. <h3>Results</h3> ABPA, OB, follicular bronchiolitis and DIPNECH shared similar physiology in this project and are compared together as Non-Asthmatic SAD (NASAD). When compared to asthmatic SAD (ASAD), NASAD demonstrated a lower FEF<sub>25–75%</sub> (NASAD range 4–26%, median 9%, 7 out of 8 &lt; 18% v. ASAD range 8–32%, median 26.5%, 1 out of 6 &lt; 18%) and a higher RV (NASAD range 74–203%, median 153%, 5 out of 8 &gt; 120% v. ASAD range 66–121%, median 97.5%, 2 out of 6 &gt; 120%). All patients, except one, demonstrated normal gas transfers strongly suggesting an absence of emphysema. HRCT alone did not provide any diagnostic benefit. Only asthma demonstrated significant and consistent bronchodilator reversibility. Tracheomalacia mimicked SAD, demonstrating an inconsistent pattern of FEF<sub>25–75%</sub> and a small degree of variation of RV around normal. Horseshoe lung demonstrated similar physiology to NASAD. <h3>Conclusions</h3> Clinicians need to consider the above mentioned diseases as an alternative diagnosis to emphysema and asthma in those with a characteristically SAD flow volume loop, a high RV and normal gas transfers.
Protective and pathological roles of nitric oxide in endotoxin shock
Authors: C E Wright, D D Rees, S Moncada
Journal: Cardiovascular Research (1992)

The aim was to investigate the effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of both the constitutive (Ca2+ dependent) and inducible (Ca2+ independent) nitric oxide (NO) synthases, or of pretreatment with the glucocorticoid dexamethasone, an inhibitor of the induction of the Ca2+ independent NO synthase, on lipopolysaccharide induced shock in the anaesthetised rabbit.Mean arterial blood pressure, and blood flow in the portal vein, hepatic artery, and hindquarter vascular beds were measured in 49 halothane anaesthetised New Zealand White rabbits given lipopolysaccharide (Salmonella minnesota, 500 micrograms.kg-1 intravenously). The effects of pre- or post-lipopolysaccharide treatment with L-NMMA (300 mg.kg-1 intravenously) and of pretreatment with dexamethasone (3 mg.kg-1 intravenously) were determined. The effect of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP, 300 micrograms.kg-1.h-1 intravenously) in animals treated with lipopolysaccharide and L-NMMA was also studied.Lipopolysaccharide elicited an initial transient fall in mean arterial pressure and decreases in blood flow in the vascular beds, followed by a progressive fall in mean arterial pressure. L-NMMA when given either before or after lipopolysaccharide markedly exacerbated its effects and resulted in severe hypotension, intense vasoconstriction, and increased mortality. Pretreatment with dexamethasone had no effect on the initial haemodynamic changes following lipopolysaccharide, but prevented the subsequent fall in mean arterial pressure observed in animals treated with lipopolysaccharide alone. Dexamethasone failed, however, to protect animals also treated with L-NMMA before lipopolysaccharide. Animals pretreated with L-NMMA and SNAP showed reduced haemodynamic changes when compared with controls (lipopolysaccharide only) or lipopolysaccharide and L-NMMA treated animals.Inhibition of both constitutive and inducible NO synthases during endotoxaemia is deleterious. This can be overcome by replacing NO intravenously with a donor of NO. Selective inhibition of the inducible NO synthase may, however, be beneficial in shock.
621 Interferon-alpha inducible gene expression in peripheral blood mononuclear cells in response to stimulation with interferon-alpha
Authors: S BEHAN, V LEROY, M OBRIEN, C OBRIEN, J HEGARTY, C OFARRELLY
Journal: Hepatology (2003)

Background/Aims: Patients with recurrent hepatitis C virus (HCV)-infection after liver transplantation (OLTx) could develop an early, multispecific, preferentially intrahepatic CD4+ T cell response. We asked now whether there is a correlation between the HCV-specific CD4+ T cell response and treatment outcome in patients who receive interferon (IFN)-α/ribavirin.Methods: Liver- and blood-derived T cell lines of 20 patients were studied in parallel before, under, at the end and after antiviral treatment. Virus-specific IFN-γ production at a single cell level to HCV-proteins (core, non-structural protein (NS)3/4, NS5) was determined by enzyme-linked immunospot assay.Results: In 6/7 non-responders a weak HCV-specific CD4+ T cell response was detectable. All six sustained responders developed a strong, at NS3/4 and NS5 directed and long-lasting CD4+ T cell response which was mainly detected in peripheral blood mononuclear cells. This reaction was significantly stronger: (1) in the responders than in the non-responders; and (2) within the responders at the end of treatment than before (P<0.03). Seven transient-responders showed a weak and/or transient HCV-specific CD4+ T cell response.Conclusions: In patients with recurrent HCV-infection after OLTx, who receive antiviral treatment, a strong, at NS3/4 and NS5 directed and long-lasting CD4+ T cell response is associated with HCV-elimination whereas no or a weak/transient response is associated with treatment failure.
The Respiratory Effects of Chloromethyl Methyl Ether
Authors: William Weiss
Journal: JAMA (1975)

A prospective study of 125 chemical workers was carried out for ten years to investigate the incidence of lung cancer. Some of the men were exposed to chloromethyl methyl ether containing bis(chloromethyl) ether as an impurity. Bronchogenic carcinoma was markedly increased among them, with a strong dose-response relationship. An unexpected inverse relationship was noted between smoking and the incidence of lung cancer. The neoplasms (all small-cell carcinomas) occurred in relatively young men. Symptoms of chronic bronchitis were reported more often among men exposed to chloromethyl methyl ether, and a dose-response relationship was apparent, with smoking a cofactor. Ventilatory function was not significantly affected by chemical exposure. Periodic screening over the first five years of the study showed a decrease in chronic coughing and an increase in dyspnea while chemical exposure was diminishing. (JAMA 234:1139-1142, 1975)
Cisplatin-Based Three Drugs Combination (NIP) as Induction and Adjuvant Treatment in Locally Advanced Non-small Cell Lung Cancer: Final Results
Authors: Maya Gottfried, Rodryg Ramlau, Maciej Krzakowski, Grzegorz Ziolo, Henryk Olechnowicz, Leona Koubkova, Jubrail Dahabreh, Aleksandra Szczesna, Guillermo Lopez Vivanco, Reury-Perng Perng, Francesco Carpagnano, Swan-Swan Leong, Alberto Fittipaldo, Cecilia De Almeida, Delphine Aubert, Dominique Grunenwald
Journal: Journal of Thoracic Oncology (2008)
Congenital Malformations
Authors: Harold Kalter, Josef Warkany
Journal: New England Journal of Medicine (1983)

IT is just over 20 years since an earlier review of ours of the causes and nature of congenital malformations appeared in these pages.1 When we wrote that report, teratology was a little-known branch of medicine, and the study of teratogenesis was the province of a limited number of scientists. Attempts were under way to discover general and specific causes of birth defects by critical evaluation of family and pregnancy histories, population data, and animal experiments. But it was already clear that the causative factors were heterogeneous and complex and that for the majority of birth defects the knowledge of . . .
DIFFERENTIAL PATTERNS OF CLINICAL PRESENTATIONS ACCORDING TO THE PATIENTS&amp;apos; AGE IN MARFAN SYNDROME
Authors: Sun-Joo Jang, Min Soo Cho, Byung Joo Sun, Dae-Hee Kim, Jong-Min Song, Duk-Hyun Kang, Jae-Kwan Song
Journal: Journal of the American College of Cardiology (2012)
MICA Polymorphism Is Associated With Type 1 Diabetes in the Korean Population
Authors: Yongsoo Park, Hongkyu Lee, Carani B. Sanjeevi, George S. Eisenbarth
Journal: Diabetes Care (2001)

OBJECTIVE— Recent studies have demonstrated that MICA (major histocompatibility complex class I chain-related genes) on the short arm of the chromosome 6 are associated with susceptibility to various autoimmune diseases in Caucasians. The aim of our study was to investigate the role of MICA in type 1 diabetes susceptibility independent of the HLA DR-DQ polymorphism in genetically distinct Koreans. RESEARCH DESIGN AND METHODS— A total of 119 patients selected from Korean Seoul type 1 diabetes registry and 134 nondiabetic unrelated control subjects were typed for exon 5 polymorphism of MICA in addition to HLA DR-DQ typing. A total of 52 simplex families of type 1 diabetes were also studied. RESULTS— The MICA microsatellite allele consisting of six repetitions of GCT/AGC (A6) was present at a significantly lower frequency in the diabetic patient group (Pc &amp;lt; 0.01; Pc = P value after Bonferroni correction) than in the control population. The MICA microsatellite allele consisting of four repetitions (A4) was present at a higher frequency in diabetic patients(P &amp;lt; 0.05). This deviated distribution was not changed even after controlling for the HLA DRB1-DQB1 haplotype. Transmission/disequilibrium test revealed significant deviation of transmission for alleles at the A6 polymorphism within the MICA gene (P &amp;lt; 0.05). CONCLUSIONS— We could assess that the MICA gene might be associated with type 1 diabetes transracially independent of the HLA gene.
A polymorphic variant inside the osteopontin gene shows association with disease course in oligoarticular juvenile idiopathic arthritis
Authors: R Marciano
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Oligoarticular onset juvenile idiopathic arthritis (JIA) has a variable disease course. In some patients the disease remains confined to a few joints (persistent oligoarticular) while in others it extends to affect more joints (oligoarticular extended). Osteopontin is thought to play a role in the pathogenesis. <b>Objective:</b> To investigate whether a polymorphic variant in the human osteopontin gene, which is in linkage disequilibrium with recently characterised promoter variants, is associated with the disease course in oligoarticular JIA. <b>Methods:</b> Genotyping of the two base pair insertion/deletion variant at +245 in the first intron was undertaken by polymerase chain reaction (PCR) amplification of DNA fragments, using a fluorescently labelled primer, followed by allele detection after rapid separation of PCR products on an automated DNA sequencer. <b>Results:</b> Allele 2 of the polymorphic variant in the osteopontin first intron was significantly associated with the persistent oligoarticular form rather than the extended form of JIA. This was verified at the level of genotype and allele frequencies. <b>Conclusions:</b> The results suggest that osteopontin gene polymorphism is associated with the disease course in oligoarticular JIA and might therefore represent a useful genetic marker to characterise patients with oligoarticular JIA who are at risk of a worse outcome.
THE PHILADELPHIA MEETING OF THE AMERICAN MEDICAL ASSOCIATION.
Authors: W. B. Atkinson
Journal: JAMA (1896)

The fact that theAmerican Medical Associationwill hold its next annual meeting in Philadelphia, thereby celebrating the semicentennial of its existence, is of interest not only to those members of the profession who already belong to theAssociation, but to those, and we believe there are many, who are desirous of entering its ranks and thereby aid in maintaining the professional standard which has so long and so successfully waved over the medical profession of this country. Fifty years ago next spring under the presidency ofDr. Jonathan Knightof Connecticut, the first great medical convention of the United States met in Philadelphia and appointed as its secretary,Dr. Alfred Stilléof that city. It also appointed as chairman of the committee on scientific papersDr. Oliver Wendell Holmes, and under the guidance of these men, well known in medicine and literature, theAssociationgained a vitality which it
RECURRENT CARCINOMA OF BREAST, WITH ROENTGEN-RAY FIBROSIS
Authors: Harold Swanberg
Journal: JAMA (1925)

Mrs. B., aged 48, referred to me, June 8, 1920, by the Mayo Clinic, for postoperative roentgen-ray therapy for carcinoma of the breast, had not had any serious previous illness, except diphtheria when a child. Her general health had always been good. She had no children. In October, 1918, she noted a small lump in the right breast, which was about the size of a quarter and was not associated with any pain. She immediately consulted a physician, and two days later had the whole breast removed, but did not have any of the axillary glands dissected, for a radical operation was not thought necessary and was not contemplated unless a pathologic examination revealed malignancy. Sections made from the growth removed were reported nonmalignant. In March, 1920, she noticed a small nodule in the skin of the right axilla. This was removed and found to be malignant. She then went
Oxidative Stress–Induced Afterdepolarizations and Calmodulin Kinase II Signaling
Authors: Lai-Hua Xie, Fuhua Chen, Hrayr S. Karagueuzian, James N. Weiss
Journal: Circulation Research (2008)

In the heart, oxidative stress caused by exogenous H(2)O(2) has been shown to induce early afterdepolarizations (EADs) and triggered activity by impairing Na current (I(Na)) inactivation. Because H(2)O(2) activates Ca(2+)/calmodulin kinase (CaMK)II, which also impairs I(Na) inactivation and promotes EADs, we hypothesized that CaMKII activation may be an important factor in EADs caused by oxidative stress. Using the patch-clamp and intracellular Ca (Ca(i)) imaging in Fluo-4 AM-loaded rabbit ventricular myocytes, we found that exposure to H(2)O(2) (0.2 to 1 mmol/L) for 5 to 15 minutes consistently induced EADs that were suppressed by the I(Na) blocker tetrodotoxin (10 micromol/L), as well as the I(Ca,L) blocker nifedipine. H(2)O(2) enhanced both peak and late I(Ca,L), consistent with CaMKII-mediated facilitation. By prolonging the action potential plateau and increasing Ca influx via I(Ca,L), H(2)O(2)-induced EADs were also frequently followed by DADs in response to spontaneous (ie, non-I(Ca,L)-gated) sarcoplasmic reticulum Ca release after repolarization. The CaMKII inhibitor KN-93 (1 micromol/L; n=4), but not its inactive analog KN-92 (1 micromol/L, n=5), prevented H(2)O(2)-induced EADs and DADs, and the selective CaMKII peptide inhibitor AIP (autocamtide-2-related inhibitory peptide) (2 micromol/L) significantly delayed their onset. In conclusion, H(2)O(2)-induced afterdepolarizations depend on both impaired I(Na) inactivation to reduce repolarization reserve and enhancement of I(Ca,L) to reverse repolarization, which are both facilitated by CaMKII activation. Our observations support a link between increased oxidative stress, CaMKII activation, and afterdepolarizations as triggers of lethal ventricular arrhythmias in diseased hearts.
Preimplantation genetic diagnosis
Authors: F. A Flinter
Journal: BMJ (2001)

Pregnant women whose babies are at risk of having a genetic condition serious enough to warrant consideration of termination of pregnancy may be offered prenatal diagnostic tests such as amniocentesis and chorionic villus biopsy. For some couples, however, such tests are not acceptable, and preimplantation genetic diagnosis is an alternative.

Preimplantation genetic diagnosis involves testing the early embryo after in vitro fertilisation. One or two cells (blastomeres) are removed at biopsy from the preimplantation embryo at the 6–10 cell stage (day 3 of development), thus allowing replacement into the uterus of unaffected embryos.

Preimplantation genetic diagnosis can be offered for three major categories of disease. Firstly, it can be used to determine the sex of the embryo for sex linked disorders where the specific genetic defect at a molecular level is unknown, highly variable, or unsuitable for testing on single cells—for example Duchenne muscular dystrophy.1 Secondly, …
Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone : a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation
Authors: M T Van Lint, C Uderzo, A Locasciulli, I Majolino, R Scimé, F Locatelli, G Giorgiani, W Arcese, A P Iori, M Falda, A Bosi, R Miniero, P Alessandrino, G Dini, B Rotoli, A Bacigalupo
Journal: Blood (1998)
Ultrasonographic Screening for Fetal Aneuploidy
Authors: John W. Seeds
Journal: New England Journal of Medicine (1997)

For decades, a maternal age of more than 35 years on the expected date of delivery has been an accepted indication for amniocentesis for fetal karyotyping, given the moderate increase in fetal aneuploidy associated with advancing maternal age. More recently, interest has grown in screening tests that might facilitate the diagnosis of fetal aneuploidy in women otherwise at low risk without excessive invasive testing. So-called triple screening is based on an association between fetal aneuploidy and a combination of low concentrations of alpha-fetoprotein and unconjugated estriol and high concentrations of chorionic gonadotropin in maternal serum. The sensitivity of this method . . .
Poisoning after One Instillation of Atropine Drops
Authors: C. M. Scally
Journal: BMJ (1936)

Poisoning after One Instillation of Atropine DropsAtropine poisoning following instillation of the, drug into the conjunctival sac is not widely recognized, though it is probably more frequent than the small number of cases recorded would suggest.A fatality is reported by Rockliffe in a sickly infant aged 10 months-the subject of congenital cataract.Three drops of 1 -per cent.atropine
Abstract LB-7: Design and development of a novel series of orally active, selective PI3Kp110β/δ inhibitors for the treatment of cancer
Authors: Stephen J. Shuttleworth
Journal: Cancer Research (2014)

Abstract The phosphatidylinositide 3-kinases (PI3Ks) have emerged as attractive therapeutic targets for the treatment of cancer. The majority of PI3K inhibitors currently in clinical development primarily target either all four class I enzymes (p110α, β, δ and γ) with limited selectivity, or are pan-class I/mTOR dual inhibitors. Over recent years, a switch of focus to more selective PI3K inhibitors for the treatment of specific tumor types has occurred. Of particular note, p110b has been reported to be the principal isoform in driving PTEN-deficient tumorigenesis; additionally, high levels of p110δ expression in solid tumor cells have been shown to suppress PTEN activity, generating cellular sensitivity to p110δ inhibition through PTEN activation. Moreover, PI3K pathway activation in certain PTEN-null solid tumors has been shown to be mediated by both the p110β and p110δ catalytic subunits, suggesting the potential of a dual-selective p110β/δ inhibitor in this setting. During the past 12 months, the discovery of activating mutant forms of both p110β and p110δ has been reported. The strategy outlined in this presentation centres on the design and development of a new class of orally-active small molecules that selectively inhibit p110β and p110δ, and which display high degrees of specificity over protein kinases and other lipid kinases. Moreover, a spectrum of p110β/δ selectivity has been achieved in this series, which has facilitated interrogation of preferred isoform inhibition profiles required to confer tumor growth inhibition; additionally, by tuning selectivity over the other class I isoforms, elimination of the mechanism-related toxicities associated with the pan-class I inhibitors currently in the clinic can be realized, making such agents potentially more conducive to combination therapy. In vitro and in vivo therapy data for advanced lead compounds will be disclosed. Citation Format: Stephen J. Shuttleworth. Design and development of a novel series of orally active, selective PI3Kp110β/δ inhibitors for the treatment of cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-7. doi:10.1158/1538-7445.AM2014-LB-7
Internists Eye Sophisticated Science
Authors: Rebecca Voelker
Journal: JAMA (1994)

BIOTECHNOLOGY. It's not just for gene splicers anymore. In the United States last year, 1300 biotechnology companies were up and running. During 1993 they raised $3 billion in new capital in the stock market, their second-best annual performance. Sales of at least two biotech drugs— erythropoietin and colony-stimulating factor—exceed $1 billion annually. So after dealing handily with the stock market and pharmaceutical development, internal medicine isn't far off on the horizon. But internists needn't become molecular experts. Awareness of diagnostic methods and treatment tools produced through biotechnology's advances is the goal. "The message for the general internist is that you can't keep up with all of it," says Ian Hart, MD, professor of medicine at the University of Ottawa (Ontario) Faculty of Medicine. Nevertheless, he detailed a sampling of new challenges and promising technologies in disease diagnosis and treatment during the annual meeting of the American College of Physicians (ACP).