tbuckley/cabot-search huggingface dataset:
Electron microscopic study on the jejunal mucosa in human cholera
Authors: H. Asakura, M. Tsuchiya, Y. Watanabe, Y. Enomoto, A. Morita, T. Morishita, H. Fukumi, M. Ohashi, A. Castro, C. Uylanogc
Journal: Gut (1974)

Small intestinal mucosa obtained from six fasting patients with cholera by a peroral biopsy technique was studied with the electron microscope. The cultures of their rectal swabs were all positive for <i>Vibrio cholerae.</i> In the absorptive cells, large pseudopod-like cytoplasmic processes with deformed microvilli or without microvilli (blebs) projected into the intestinal lumen from the apical cell surface, interrupting the microvillous border. In the crypts some of the undifferentiated crypt cells possessed pseudopod-like cytoplasmic projections which extended into the crypt lumen. The swelling of mitochondria, the disappearance of their cristae, an increase in the number of vesicles of the Golgi apparatus, and the dilatation and vesiculation of endoplasmic reticulum were observed in the epithelial cells. The apical portion of the cells became oedematous in some of the epithelial cells. Cytoplasmic fragments enclosed by a plasma membrane, desquamated epithelial cells, cytoplasmic organelles, and secretory granules were lying free in the intestinal lumen. Marked irregular widening of the interepithelial spaces in the jejunal mucoa was observed at the midvillous area. Many cystic vacuoles were present in the cytoplasm of epithelial cells. The possibility of fluids being transported from blood vessels to intestinal lumina through the interepithelial spaces, and the significance of these pathological findings in human cholera are discussed in this study.
Novel psychoactive substances of interest for psychiatry
Authors: Fabrizio Schifano, Laura Orsolini, G. Duccio Papanti, John M. Corkery
Journal: World Psychiatry (2015)

Novel psychoactive substances include synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, phencyclidine-like dissociatives, piperazines, GABA-A/B receptor agonists, a range of prescribed medications, psychoactive plants/herbs, and a large series of performance and image enhancing drugs. Users are typically attracted by these substances due to their intense psychoactive effects and likely lack of detection in routine drug screenings. This paper aims at providing psychiatrists with updated knowledge of the clinical pharmacology and psychopathological consequences of the use of these substances. Indeed, these drugs act on a range of neurotransmitter pathways/receptors whose imbalance has been associated with psychopathological conditions, including dopamine, cannabinoid CB1, GABA-A/B, 5-HT2A, glutamate, and k opioid receptors. An overall approach in terms of clinical management is briefly discussed.
Treatment of chronic hepatitis C with consensus interferon: A multicenter, randomized, controlled trial
Authors: M J Tong, K R Reddy, W M Lee, P J Pockros, J C Hoefs, E B Keeffe, F B Hollinger, E J Hathcote, H White, R T Foust, D M Jensen, E L Krawitt, H Fromm, M Black, L M Blatt, M Klein, J Lubina
Journal: Hepatology (1997)

This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-α2b). Patients were randomized to receive CIFN at doses of 3 μg or 9 μg, or 15 μg IFN-α2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse- transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-μg dose than the 3- μg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-μg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-μg IFN-α2b cohort. However, patients receiving 9 μg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 μg IFN- α2b over the course of treatment ( P &lt; .01). Similarly, analysis of patients infected with HCV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9- μg CIFN group when compared with the 15-μg IFN-α2b group ( P &lt; .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 μg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-μg IFN-α2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse- events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 μg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.
Simulation of cardiac pathologies using an electromechanical biventricular model and XMR interventional imaging
Authors: M. Sermesant, K. Rhode, G.I. Sanchez-Ortiz, O. Camara, R. Andriantsimiavona, S. Hegde, D. Rueckert, P. Lambiase, C. Bucknall, E. Rosenthal, H. Delingette, D.L.G. Hill, N. Ayache, R. Razavi
Journal: Medical Image Analysis (2005)
Racial Disparities in Quality-Adjusted Life-Years Associated With Diabetes and Visual Impairment
Authors: Kathryn E. McCollister, D. Diane Zheng, Cristina A. Fernandez, David J. Lee, Byron L. Lam, Kristopher L. Arheart, Anat Galor, Manuel Ocasio, Peter Muennig
Journal: Diabetes Care (2012)

OBJECTIVE Compare differences in health-related quality of life among blacks and whites to examine if race, diabetes, and visual impairment (VI) present a triple disadvantage in terms of quality-adjusted life expectancy. RESEARCH DESIGN AND METHODS Data were analyzed from the 2000–2003 Medical Expenditure Panel Survey, a nationally representative survey that contains the EuroQol 5D (EQ-5D). The EQ-5D generates health utility values that provide a measure of the morbidity associated with various health states, such as having moderate or severe problems with mobility. The EQ-5D score can be linked with life expectancy data to calculate quality-adjusted life-years (QALYs), the number of years of optimal health an individual is expected to live. Multivariate analyses were conducted to estimate and compare differences in QALYs by diabetes status, VI status, and race. RESULTS Whites had a higher quality-adjusted life expectancy across all diabetes/VI comparisons. Overall, blacks with diabetes and VI had the fewest number of QALYs remaining (19.6 years), and whites with no impairment had the greatest number of QALYs remaining (31.6 years). Blacks with diabetes only had 1.7 fewer years of optimal health (fewer QALYs) than whites with diabetes. Within individuals with both diabetes and VI, however, this gap more than doubled, with blacks experiencing 3.5 fewer QALYs than whites. CONCLUSIONS Although efforts to target and reduce racial health disparities associated with diabetes appear to be effective, black communities may be contributing to a greater overall burden of illness given poorer infrastructure and less accommodation for disabilities such as VI.
PREPARATION AND PROPERTIES OF A PROTEIN (R ANTIGEN) OCCURRING IN STREPTOCOCCI OF GROUP A, TYPE 28 AND IN CERTAIN STREPTOCOCCI OF OTHER SEROLOGICAL GROUPS
Authors: Rebecca C. Lancefield, Gertrude E. Perlmann
Journal: The Journal of Experimental Medicine (1952)

A group A, type 28 protein antigen, resistant to tryptic digestion and previously considered to be a type-specific substance, was purified and its chemical and immunological properties studied. This protein lacks the characteristic properties of a type-specific M antigen since it is apparently unrelated to virulence and does not induce the formation of protective antibodies although precipitins are readily produced. It is designated the R antigen. The R antigen in addition to occurring in "type 28" group A strains also occurs in some strains of streptococci of other serological groups. Protective antibodies, distinct from precipitins for the R antigen, are present in "type 28" antibacterial sera. The antigens responsible for protection have not been identified, and it is possible that several different types may be included among strains designated as type 28 on the basis of the R antigen. The purified R antigen is phosphorus-free and has a sulphur content of 1.04 per cent. In the ultraviolet a maximum absorption was obtained at a wave length of 280 mµ and a minimum at 254 mµ. Electrophoretically the R antigen was found to be 95 per cent homogeneous at most pH values, but at pH 4.6 the main peak separated into two peaks of approximately equal areas, both containing serologically active material. The interpretation of this finding is at present uncertain. The isoelectric pH was at 4.5 in sodium acetate buffer of 0.1 ionic strength. The purified R antigen sedimented in the ultracentrifuge as a single boundary.
Polymorphisms of the mannose binding lectin gene in patients with Sjogren's syndrome
Authors: Z-Y Wang
Journal: Annals of the Rheumatic Diseases (2001)

To investigate polymorphisms of both codon 54 allele and promoter variants of the mannose binding lectin (MBL) gene in patients with primary Sjögren's syndrome (SS).Polymorphisms of codon 54 allele and promoter variants of the MBL gene in 104 patients with SS and 143 healthy controls were determined by polymerase chain reaction-restriction fragment length polymorphism and allele specific polymerase chain reaction respectively.The allele frequency of the wild type of MBL codon 54 was significantly higher in patients with SS than in controls (0.836 v 0.741; p=0.011), and the frequency of the homozygous wild type of MBL codon 54 was significantly higher in patients with SS than in controls (0.692 v 0.539; p=0.024). On the other hand, the allele frequencies of the MBL promoter gene did not differ between patients and controls (chi(2)=4.01, df=2, p=0.135).The polymorphism of the MBL gene may be one of the genetic factors that determines susceptibility to SS.
Patient-Physician Communication About Health-Related Quality-of-Life Problems: Are Non-Hodgkin Lymphoma Survivors Willing to Talk?
Authors: Neeraj K. Arora, Roxanne E. Jensen, Nadiyah Sulayman, Ann S. Hamilton, Arnold L. Potosky
Journal: Journal of Clinical Oncology (2013)

To investigate non-Hodgkin lymphoma (NHL) survivors' willingness to discuss health-related quality-of-life (HRQOL) problems with their follow-up care physician.Willingness to discuss HRQOL problems (physical, daily, emotional, social, and sexual functioning) was examined among 374 NHL survivors, 2 to 5 years postdiagnosis. Survivors were asked if they would bring up HRQOL problems with their physician and indicate reasons why not. Logistic regression models examined the association of patient sociodemographics, clinical characteristics, follow-up care variables, and current HRQOL scores with willingness to discuss HRQOL problems.Overall, 94%, 82%, 76%, 43%, and 49% of survivors would initiate discussions of physical, daily, emotional, social, and sexual functioning, respectively. Survivors who indicated their physician "always" spent enough time with them or rated their care as "excellent" were more willing to discuss HRQOL problems (P < .05). Survivors reporting poorer physical health were less willing to discuss their daily functioning problems (P < .001). Men were more willing to discuss sexual problems than women (P < .001). One in three survivors cited "nothing can be done" as a reason for not discussing daily functioning problems, and at least one in four cited "this was not their doctor's job" and a preference to "talk to another clinician" as reasons for not discussing emotional, social, and sexual functioning.NHL survivors' willingness to raise HRQOL problems with their physician varied by HRQOL domain. For some domains, even when survivors were experiencing problems, they may not discuss them. To deliver cancer care for the whole patient, interventions that facilitate survivor-clinician communication about survivors' HRQOL are needed.
Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome in the context of inherited lipodystrophies
Authors: Frederic Reinier, Magdalena Zoledziewska, David Hanna, Josh D. Smith, Maria Valentini, Ilenia Zara, Riccardo Berutti, Serena Sanna, Manuela Oppo, Roberto Cusano, Rosanna Satta, Maria Antonietta Montesu, Chris Jones, Decio Cerimele, Deborah A. Nickerson, Andrea Angius, Francesco Cucca, Francesca Cottoni, Laura Crisponi
Journal: Metabolism (2015)
Apatinib (YN968D1) Reverses Multidrug Resistance by Inhibiting the Efflux Function of Multiple ATP-Binding Cassette Transporters
Authors: Yan-jun Mi, Yong-ju Liang, Hong-bing Huang, Hong-yun Zhao, Chung-Pu Wu, Fang Wang, Li-yang Tao, Chuan-zhao Zhang, Chun-Ling Dai, Amit K. Tiwari, Xiao-xu Ma, Kenneth Kin Wah To, Suresh V. Ambudkar, Zhe-Sheng Chen, Li-wu Fu
Journal: Cancer Research (2010)

Apatinib, a small-molecule multitargeted tyrosine kinase inhibitor, is in phase III clinical trial for the treatment of patients with non-small-cell lung cancer and gastric cancer in China. In this study, we determined the effect of apatinib on the interaction of specific antineoplastic compounds with P-glycoprotein (ABCB1), multidrug resistance protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2). Our results showed that apatinib significantly enhanced the cytotoxicity of ABCB1 or ABCG2 substrate drugs in KBv200, MCF-7/adr, and HEK293/ABCB1 cells overexpressing ABCB1 and in S1-M1-80, MCF-7/FLV1000, and HEK293/ABCG2-R2 cells overexpressing ABCG2 (wild-type). In contrast, apatinib did not alter the cytotoxicity of specific substrates in the parental cells and cells overexpressing ABCC1. Apatinib significantly increased the intracellular accumulation of rhodamine 123 and doxorubicin in the multidrug resistance (MDR) cells. Furthermore, apatinib significantly inhibited the photoaffinity labeling of both ABCB1 and ABCG2 with [(125)I]iodoarylazidoprazosin in a concentration-dependent manner. The ATPase activity of both ABCB1 and ABCG2 was significantly increased by apatinib. However, apatinib, at a concentration that produced a reversal of MDR, did not significantly alter the ABCB1 or ABCG2 protein or mRNA expression levels or the phosphorylation of AKT and extracellular signal-regulated kinase 1/2 (ERK1/2). Importantly, apatinib significantly enhanced the effect of paclitaxel against the ABCB1-resistant KBv200 cancer cell xenografts in nude mice. In conclusion, apatinib reverses ABCB1- and ABCG2-mediated MDR by inhibiting their transport function, but not by blocking the AKT or ERK1/2 pathway or downregulating ABCB1 or ABCG2 expression. Apatinib may be useful in circumventing MDR to other conventional antineoplastic drugs.
Dermatological complications and safety of anti-TNF treatments
Authors: J. F. Kerbleski, A. B. Gottlieb
Journal: Gut (2009)

It has been reported that tumour necrosis factor (TNF) inhibitors have adverse side-effects including infections, malignancies, demyelinating disease, and induction of autoimmune conditions. Dermatological complications of anti-TNF therapy include injection site reactions, cutaneous infections, allergic rashes, psoriasis, non-melanoma skin cancer (NMSC), and rare reports of lupus-like syndrome, erythema multiforme (EM), Steven’s Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).

Currently, there are four TNF inhibitors approved by the US Federal Drug Administration (FDA): etanercept (Enbrel; Amgen, Thousand Oaks, California, USA, and Wyeth Pharmaceuticals, Philadelphia, USA), infliximab (Remicade; Centacor, Horsham, Philadelphia, USA), adalimumab (Humira; Abbott Laboratories, Abbott Park, Illinois, USA), and certolizumab pegol (Cimzia; UCB, Smyrna, Georgia, USA). They are prescribed for and have revolutionised the treatment of various immune-mediated inflammatory disorders, most notably Crohn’s disease, ulcerative colitis, rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, and ankylosing spondylitis (AS). Almost 2 million patients worldwide have been treated with them since their introduction.1

Although TNF inhibitors exhibit impressive efficacy, a number of dermatological complications exist: injection site reactions, allergic rashes, cutaneous manifestations of infusion reactions, cutaneous infections, psoriasis, NMSCs, and rare lesions including lupus-like syndrome, EM, SJS, TEN, and cutaneous vasculitis. Indeed, two recent prospective studies of 289 and 150 rheumatological patients started on TNF inhibitors found that 23–25% had a dermatological complication.2 3

The following is a review of safety data based upon reports from the FDA, review articles, company data, and reports from the German Register and from the British Society for Rheumatology Biologics Register (BSRBR). Management of these reactions is presented extensively elsewhere and briefly discussed in each section, the final table, and the conclusion.

Injection site reactions occur with the use of etanercept, adalimumab and certolizumab pegol. Signs and symptoms include redness, itching, bruising, pain, swelling and/or irritation at the site of injection. These occurred more often …
Effects of Cancer-Associated EPHA3 Mutations on Lung Cancer
Authors: Guanglei Zhuang, Wenqiang Song, Katherine Amato, Yoonha Hwang, Keunwook Lee, Mark Boothby, Fei Ye, Yan Guo, Yu Shyr, Luping Lin, David P. Carbone, Dana M. Brantley-Sieders, Jin Chen
Journal: JNCI Journal of the National Cancer Institute (2012)

Cancer genome sequencing efforts recently identified EPHA3, which encodes the EPHA3 receptor tyrosine kinase, as one of the most frequently mutated genes in lung cancer. Although receptor tyrosine kinase mutations often drive oncogenic conversion and tumorigenesis, the oncogenic potential of the EPHA3 mutations in lung cancer remains unknown. We used immunoprecipitation, western blotting, and kinase assays to determine the activity and signaling of mutant EPHA3 receptors. A mutation-associated gene signature was generated from one large dataset, mapped to another training dataset with survival information, and tested in a third independent dataset. EPHA3 expression levels were determined by quantitative reverse transcription-polymerase chain reaction in paired normal-tumor clinical specimens and by immunohistochemistry in human lung cancer tissue microarrays. We assessed tumor growth in vivo using A549 and H1299 human lung carcinoma cell xenografts in mice (n = 7–8 mice per group). Tumor cell proliferation was measured by bromodeoxyuridine incorporation and apoptosis by multiple assays. All P values are from two-sided tests. At least two cancer-associated EPHA3 somatic mutations functioned as dominant inhibitors of the normal (wild type) EPHA3 protein. An EPHA3 mutation–associated gene signature that was associated with poor patient survival was identified. Moreover, EPHA3 gene copy numbers and/or expression levels were decreased in tumors from large cohorts of patients with lung cancer (eg, the gene was deleted in 157 of 371 [42%] primary lung adenocarcinomas). Reexpression of wild-type EPHA3 in human lung cancer lines increased apoptosis by suppression of AKT activation in vitro and inhibited the growth of tumor xenografts (eg, for H1299 cells, mean tumor volume with wild-type EPHA3 = 437.4mm3 vs control = 774.7mm3, P < .001). Tumor-suppressive effects of wild-type EPHA3 could be overridden in trans by dominant negative EPHA3 somatic mutations discovered in patients with lung cancer. Cancer-associated EPHA3 mutations attenuate the tumor-suppressive effects of normal EPHA3 in lung cancer.
Aortic Lipoprotein Lipase Activity in Relation to Species, Age, Sex, and Blood Pressure
Authors: SAMUEL MALLOV
Journal: Circulation Research (1964)

It has been suggested that lipoprotein lipase (LPL) activity may play a role in the etiology of atherosclerosis. To determine whether there is an inverse relationship between arterial LPL activity and the tendency for arteries to become atherosclerotic, determinations were made of the activities of the enzyme in homogenates of the aortas of animals under conditions associated with a greater or lesser tendency for atherosclerosis to develop. It was found that the LPL activities of the aortas of old rats and rabbits were significantly lower than those of young animals of the same species, respectively. Rats, which are resistant to the development of atherosclerosis, manifested about twice the aortic LPL activities that rabbits did, the latter animals being notorious for the ease with which they develop the disease. This was true regardless of the age and sex of the animals compared. These results support the hypothesis that low arterial LPL activity may be associated with increased atherogenesis. Aortas of female rats or rabbits, however, showed no greater LPL activities than did aortas of males of the same species. Renal and desoxycorticosterone-salt hypertensions were accompanied by significant increases rather than decreases in aortic LPL activity. The latter results are not consonant with the aforementioned hypothesis.
Randomized Phase III Trial of Sequential Chemoradiotherapy Compared With Concurrent Chemoradiotherapy in Locally Advanced Non–Small-Cell Lung Cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique–Groupe Français de Pneumo-Cancérologie NPC 95-01 Study
Authors: Pierre Fournel, Gilles Robinet, Pascal Thomas, Pierre-Jean Souquet, Hervé Léna, Alain Vergnenégre, Jean-Yves Delhoume, Jacques Le Treut, Jules-Antoine Silvani, Eric Dansin, Marie-Cécile Bozonnat, Jean-Pierre Daurés, Françoise Mornex, Maurice Pérol
Journal: Journal of Clinical Oncology (2005)

We conducted a phase III study to compare the survival impact of concurrent versus sequential treatment with radiotherapy (RT) and chemotherapy (CT) in unresectable stage III non-small-cell lung cancer (NSCLC).Patients were randomly assigned to one of the two treatment arms. In the sequential arm, patients received induction CT with cisplatin (120 mg/m2) on days 1, 29, and 57, and vinorelbine (30 mg/m2/wk) from day 1 to day 78, followed by thoracic RT at a dose of 66 Gy in 33 fractions (2 Gy per fraction and 5 fractions per week). In the concurrent arm, the same RT was started on day 1 with two concurrent cycles of cisplatin 20 mg/m2/d and etoposide 50 mg/m2/d (days 1 to 5 and days 29 to 33); patients then received consolidation therapy with cisplatin 80 mg/m2 on days 78 and 106 and vinorelbine 30 mg/m2/wk from days 78 to 127.Two hundred five patients were randomly assigned. Pretreatment characteristics were well balanced between the two arms. There were six toxic deaths in the sequential arm and 10 in the concurrent arm. Median survival was 14.5 months in the sequential arm and 16.3 months in the concurrent arm (log-rank test P = .24). Two-, 3-, and 4-year survival rates were better in the concurrent arm (39%, 25%, and 21%, respectively) than in the sequential arm (26%, 19%, and 14%, respectively). Esophageal toxicity was significantly more frequent in the concurrent arm than in the sequential arm (32% v 3%).Although not statistically significant, clinically important differences in the median, 2-, 3-, and 4-year survival rates were observed, with a trend in favor of concurrent chemoradiation therapy, suggesting that is the optimal strategy for patients with locally advanced NSCLC.