tbuckley/cabot-search huggingface dataset:
RNA Interference Therapy in Lung Transplant Patients Infected with Respiratory Syncytial Virus
Authors: Martin R. Zamora, Marie Budev, Mark Rolfe, Jens Gottlieb, Atul Humar, John DeVincenzo, Akshay Vaishnaw, Jeffrey Cehelsky, Gary Albert, Sara Nochur, Jared A. Gollob, Allan R. Glanville
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Lower respiratory tract infections due to respiratory syncytial virus (RSV) are associated with development of bronchiolitis obliterans syndrome in lung transplant (LTX) recipients. ALN-RSV01 is a small interfering RNA targeting RSV replication.To determine the safety and explore the efficacy of ALN-RSV01 in RSV infection.We performed a randomized, double-blind, placebo-controlled trial in LTX recipients with RSV respiratory tract infection. Patients were permitted to receive standard of care for RSV. Aerosolized ALN-RSV01 (0.6 mg/kg) or placebo was administered daily for 3 days. Viral load was determined by quantitative reverse transcriptase-polymerase chain reaction on serial nasal swabs. Patients completed symptom score cards twice daily. Lung function, including the incidence of new-onset or progressive bronchiolitis obliterans syndrome, was recorded at Day 90.We enrolled 24 patients (ALN-RSV01, n = 16; placebo, n = 8); randomization was stratified by ribavirin use. ALN-RSV01 was well tolerated, with no drug-related serious adverse events or post-inhalation perturbations in lung function. Interpretation of viral measures was confounded by baseline differences between the two groups in viral load and time from symptom onset to first dose. Mean daily symptom scores were lower in subjects receiving ALN-RSV01, and the mean cumulative daily total symptom score was significantly lower with ALN-RSV01 (114.7 ± 63.13 vs. 189.3 ± 99.59, P = 0.035). At Day 90, incidence of new or progressive bronchiolitis obliterans syndrome was significantly reduced in ALN-RSV01 recipients compared with placebo (6.3% vs. 50%, P = 0.027).ALN-RSV01 was safe and may have beneficial effects on long-term allograft function in LTX patients infected with RSV. Clinical trial registered with www.clinicaltrials.gov (NCT 00658086).
Argentina: torture, silence, and medical teaching
Authors: L. Justo
Journal: BMJ (2003)

More than 30 years ago I asked my surgical instructor about petechial lesions on the scrotums of some criminals interned in the surgical ward. The shocking answer was, “Oh, yes, the police make them all go through ‘the machine’ before taking them to the hospital.” The machine, the “picana electrica,” was a device for torturing prisoners with electric shocks, usually in the vagina, testicles, mouth, anus, or nipples. I was horrified by the fact itself but no less by the matter of fact tone in which the answer was given. As a medical student I was pretty powerless, but I went to the head of the surgical service and tried to lodge a formal complaint. I was rebuffed without any chance to make my argument heard.

Since 1983 we have been living under a “democratic” government, but torture is still rampant in Argentina. Sergio Gustavo Duran was arrested by the police in 1992. He was 17 years old. The arrest was routine—he wasn't …
Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function
Authors: Tristan M Robinson, Dean A Sewell, Anna Casey, Gery Steenge, Paul L Greenhaff
Journal: British Journal of Sports Medicine (2000)

Background —The use of creatine (Cr) as a nutritional supplement to aid athletic performance has gained widespread popularity among athletes. However, concerns have recently been expressed over potentially harmful effects of short and long term Cr supplementation on health. Methods —Forty eight young healthy subjects were randomly allocated to three experimental protocols aimed at elucidating any potential health risks associated with five days (20 g/day) to nine weeks (3 g/day) of Cr supplementation. Venous blood samples were collected before and after periods of Cr supplementation and were analysed for some haematological indices, and for indices of hepatic, muscular, and renal dysfunction. Findings —All measured indices were well within their respective normal range at all times. Serum creatinine concentration tended to be increased the day after Cr supplementation. However, values had returned to baseline six weeks after the cessation of supplementation. These increases were probably attributable to increased creatinine production rather than renal dysfunction. No indication of impairment to the haematological indices measured, hepatic function, or muscle damage was apparent after Cr supplementation. Interpretation —These data provide evidence that there are no obvious adverse effects of acute or more chronic Cr supplementation on the haematological indices measured, nor on hepatic, muscle, and renal function. Therefore there is no apparent health risk associated with Cr supplementation to healthy people when it is ingested in quantities that have been scientifically proven to increase muscle Cr stores.
Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel diseases.
Authors: B S Nielsen, N Borregaard, J R Bundgaard, S Timshel, M Sehested, L Kjeldsen
Journal: Gut (1996)

In inflammatory and neoplastic disorders of the colon a defect barrier function of the mucosa may result in absorption of bacterial products from the intestinal lumen. These products may further recruit inflammatory cells and thus augment the inflammatory response. A novel lipocalin in neutrophils, neutrophil gelatinase associated lipocalin (NGAL), with the ability to bind bacterial formylpeptides, has been described and therefore it is of interest to investigate the expression of this protein in diseases of the colon. Expression of NGAL was investigated by immunohistochemistry and by mRNA in situ hybridisation in normal colon and in neoplastic and inflammatory colorectal diseases. A very high expression of NGAL was seen in colonic epithelium in areas of inflammation, both in non-malignant epithelium (diverticulitis, inflammatory bowel disease, and appendicitis) as well as in premalignant and malignant neoplastic lesions of the colon. In adenocarcinoma, the NGAL expression was especially abundant in the transitional mucosa and in the superficial ulcerated area. On the other hand, no NGAL expression could be detected in lymph node metastases from these adenocarcinomas. A weak expression of NGAL in some epithelial cells was only occasionally seen in normal colon. In conclusion, NGAL synthesis is induced in epithelial cells in inflammatory and neoplastic, colorectal diseases. NGAL may serve an important anti-inflammatory function as a scavenger of bacterial products.
Epithelial-Mesenchymal Transition in Breast Cancer Relates to the Basal-like Phenotype
Authors: David Sarrió, Socorro María Rodriguez-Pinilla, David Hardisson, Amparo Cano, Gema Moreno-Bueno, José Palacios
Journal: Cancer Research (2008)

Epithelial-mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. In carcinoma cells, EMT can be associated with increased aggressiveness, and invasive and metastatic potential. To assess the occurrence of EMT in human breast tumors, we conducted a tissue microarray-based immunohistochemical study in 479 invasive breast carcinomas and 12 carcinosarcomas using 28 different markers. Unsupervised hierarchical clustering of the tumors and statistical analysis showed that up-regulation of EMT markers (vimentin, smooth-muscle-actin, N-cadherin, and cadherin-11) and overexpression of proteins involved in extracellular matrix remodeling and invasion (SPARC, laminin, and fascin), together with reduction of characteristic epithelial markers (E-cadherin and cytokeratins), preferentially occur in breast tumors with the "basal-like phenotype." Moreover, most breast carcinosarcomas also had a basal-like phenotype and showed expression of mesenchymal markers in their sarcomatous and epithelial components. To assess whether basal-like cells have intrinsic phenotypic plasticity for mesenchymal transition, we performed in vitro studies with the MCF10A cell line. In response to low cell density, MCF10A cells suffer spontaneous morphologic and phenotypic EMT-like changes, including cytoskeleton reorganization, vimentin and Slug up-regulation, cadherin switching, and diffuse cytosolic relocalization of the catenins. Moreover, these phenotypic changes are associated with modifications in the global genetic differentiation program characteristic of the EMT process. In summary, our data indicate that in breast tumors, EMT likely occurs within a specific genetic context, the basal phenotype, and suggests that this proclivity to mesenchymal transition may be related to the high aggressiveness and the characteristic metastatic spread of these tumors.
The drooling child
Authors: A. K. Dritsoula, D. Greenstreet, M. S. Thevasagayam
Journal: BMJ (2015)

The parents of a 4 year old child present with concerns about drooling. Severe drooling may be associated with comorbidities, such as cerebral palsy, severe mental retardation, and hypoxic encephalopathy, and affects the wellbeing of children with disabilities as well as increasing the demand on their carers. Treatment improves children’s quality of life and reduces their care burden.1 2
Abnormal Transradiancy of One Lung
Authors: W. M. Macleod
Journal: Thorax (1954)

Coronary blood flow is dependent upon arterial pressure, diastolic time, and small vessel resistance. The system is regulated to achieve a low flow high oxygen extraction and low myocardial Po<sub>2</sub>. <i>This setting is sensitive to change in oxygen needs. Regulation of blood flow occurs primarily through local intrinsic regulation, most likely through production of vasodilating metabolites in response to minimal degrees of ischaemia. Local regulation appears to dominate over remote regulation in most circumstances. Blood flow distribution to the myocardium is depth dependent as well as regional in variation. Both types of distribution of blood flow are profoundly disturbed in the presence of obstructive coronary atherosclerosis. This results in either concentric myocardial shells or patchy transmural zones of selective ischaemia with clear-cut but local abnormalities in metabolism and performance</i>.
COMT Haplotypes Modulate Associations of Antenatal Maternal Anxiety and Neonatal Cortical Morphology
Authors: Anqi Qiu, Ta Anh Tuan, Mei Lyn Ong, Yue Li, Helen Chen, Anne Rifkin-Graboi, Birit F.P. Broekman, Kenneth Kwek, Seang-Mei Saw, Yap-Seng Chong, Peter D. Gluckman, Marielle V. Fortier, Joanna Dawn Holbrook, Michael J. Meaney
Journal: American Journal of Psychiatry (2014)

Objective: Exposure to antenatal maternal anxiety and complex genetic variations may shape fetal brain development. In particular, the catechol-O-methyltransferase (COMT) gene, located on chromosome 22q11.2, regulates catecholamine signaling in the prefrontal cortex and is implicated in anxiety, pain, and stress responsivity. This study examined whether individual single-nucleotide polymorphisms (SNPs) of the COMT gene and their haplotypes moderate the association between antenatal maternal anxiety and in utero cortical development. Method: A total of 146 neonates were genotyped and underwent MRI shortly after birth. Neonatal cortical morphology was characterized using cortical thickness. Antenatal maternal anxiety was assessed using the State-Trait Anxiety Inventory at week 26 of pregnancy. Results: Individual COMT SNPs (val158met, rs737865, and rs165599) modulated the association between antenatal maternal anxiety and the prefrontal and parietal cortical thickness in neonates. Based on haplotype trend regression analysis, findings also showed that among rs737865-val158met-rs165599 haplotypes, the A-val-G (AGG) haplotype probabilities modulated positive associations of antenatal maternal anxiety with cortical thickness in the right ventrolateral prefrontal cortex and the right superior parietal cortex and precuneus. In contrast, the G-met-A (GAA) haplotype probabilities modulated negative associations of antenatal maternal anxiety with cortical thickness in bilateral precentral gyrus and the dorsolateral prefrontal cortex. Conclusions: These results suggest that the association between maternal anxiety and in utero neurodevelopment is modified through complex genetic variation in COMT. Such genetic moderation may explain, in part, the variation in phenotypic outcomes in offspring associated with maternal emotional well-being.
Evidence for concerted effects of aldosterone on a target sodium-transporting epithelium.
Authors: R Beauwens, J Crabbé
Journal: Journal of Clinical Investigation (1983)

The sodium-transporting activity of toad skin is stimulated in vitro with aldosterone in the absence of energy-providing substrate; it can be stimulated further upon addition of glucose after prolonged (overnight) incubation. The magnifying effect exerted by glucose in these conditions could be blocked by inhibitors of ribonucleic acid and protein biosynthesis. In addition, exposure to cycloheximide prevented the increase in thermodynamic affinity resulting from aldosterone treatment. A synthetic 19-nor steroid, (RU 24411), dimethyl-2,2-hydroxy-21-nor-19-pregnene-4-dione-3,20, also stimulated sodium transport by toad skin incubated in the absence of glucose, but there was no magnifying effect of this substrate. Furthermore, there was no change in thermodynamic affinity with RU 24411. Therefore, the magnifying effect seen with glucose and the increase in thermodynamic affinity are not necessarily integral parts of the response of sodium-transporting epithelial to "mineralocorticoids."
Preservation of intraalveolar surfactant in a rat lung ischaemia/reperfusion injury model
Authors: M. Ochs, H. Fehrenbach, I. Nenadic, T. Bando, A. Fehrenbach, D. Schepelmann, J.M. Albes, T Wahlers, J Richter
Journal: European Respiratory Journal (2000)

Ischaemia/reperfusion (I/R) injury, a major problem in clinical lung transplantation, is associated with surfactant dysfunction. The present study aimed to test the hypothesis that preservation related improvements in post-ischaemic lung function are associated with improved ultrastructural preservation of pulmonary surfactant. Rat lungs were flush perfused with modified Euro-Collins solutions (ECS), stored for 2 h at 4 degrees C, and reperfused for 40 min. Lungs were preserved with conventional (ECS 115: 115 mmol x L(-1) K+), medium-K+ (ECS 40: 40 mmol x L(-1) K+), or low-K+ (ECS 10: 10 mmol x L(-1) K+) ECS. Functional parameters were monitored during reperfusion (n=10 per group). After reperfusion, left lungs were prepared for electron microscopical and stereological analysis of surfactant (n=5 per group). In all three experimental groups notable I/R injury developed which was lowest in ECS 40 as indicated by significantly less intraalveolar oedema, higher perfusate oxygenation, and lower peak inspiratory pressure. This was associated with a significantly superior preservation of the ultrastructure of the surface active surfactant subtype tubular myelin in ECS 40 compared with ECS 115 and ECS 10. Stereological analysis revealed that the relative amount of tubular myelin was highest in ECS 40 (mean+/-SEM; 6.2+/-0.8%) compared with ECS 115 (3.0+/-1.0%) and ECS 10 (2.7+/-1.6%). Analysis of surfactant in its natural location within the organ showed that the severity of ischaemia/reperfusion injury correlates with differences in intraalveolar surfactant composition. Improved post-ischaemic respiratory function achieved by medium-K+ Euro-Collins solution is associated with superior ultrastructural preservation of tubular myelin. It is concluded that the integrity of surface active tubular myelin represents an important criterion for the assessment of lung preservation quality.
Hearing Addresses Condoms for HPV Prevention
Authors: A. Christopher
Journal: JNCI Journal of the National Cancer Institute (2004)

A politically challenged debate about labeling condoms with warnings about the link between human papillomavirus (HPV) and cervical cancer has erupted following a related Congressional hearing on the issue in March. Although the dispute centers on the protection of women from cervical cancer the debate is just as much about ideology: premarital abstinence or monogamy in marriage versus condom use for those who choose to be sexually active. The hearings called by Rep. Mark Souder (R-lnd.) at the urging of Tom Coburn M.D. co-chair of the Presidential Advisory Committee on HIV/AIDS continue to raise questions about a public law Coburn authored in 2000 and that former President Bill Clinton signed days before leaving office. Souder confronted the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention with his belief that the agencies had not complied with the public law.  (excerpt)
The management of acute testicular pain in children and adolescents
Authors: M. T. Jefferies, A. C. Cox, A. Gupta, A. Proctor
Journal: BMJ (2015)

<sup>68</sup>Ga-labeled somatostatin analog (SSA) PET/CT is now a standard-of-care component in the management of neuroendocrine tumors (NETs). However, treatment response for NETs is still assessed with morphologic size measurements from other modalities, which can result in inaccuracy about the disease burden. Functional tumor volume (FTV) acquired from SSA PET/CT has been suggested as a possible metric, but no validated measurement tool to measure FTV exists. We tested the precision of multiple FTV computational approaches compared with morphologic volume measurements to identify a candidate for incorporation into future FTV studies to assess tumor burden more completely and accurately. <b>Methods:</b> The clinical and imaging data of 327 NET patients were collected at Memorial Sloan Kettering Cancer Center between December 2016 and April 2018. Patients were required to have SSA PET/CT and dedicated CT scans within 6 wk and were excluded if they had any intervention between scans. When paired studies were evaluated, 150 correlating lesions demonstrated SSA. Lesions were excluded if they contained necrotic components or were lobulated. This exclusion resulted in 94 lesions in 20 patients. The FTV for each lesion was evaluated with a hand-drawn assessment and 3 automated techniques: 50% threshold from SUV<sub>max</sub>, 42% threshold from SUV<sub>max</sub>, and background-subtracted lesion activity. These measurements were compared with volume calculated from morphologic volume measurements. <b>Results:</b> The FTV calculation methods showed varying correlations with morphologic volume measurements. FTV using a 42% threshold had a 0.706 correlation, hand-drawn volume from PET imaging had a 0.657 correlation, FTV using a 50% threshold had a 0.645 correlation, and background-subtracted lesion activity had a 0.596 correlation. The Bland–Altman plots indicated that all FTV methods had a positive mean difference from morphologic volume, with a 50% threshold showing the smallest mean difference. <b>Conclusion:</b> FTV determined with thresholding of SUV<sub>max</sub> demonstrated the strongest correlation with traditional morphologic lesion volume assessment and the least bias. This method was more accurate than FTV calculated from hand-drawn volume assessments. Threshold-based automated FTV assessment promises to better determine disease extent and prognosis in patients with NETs.
Lactic Acidosis and Hepatic Steatosis Associated with Use of Stavudine: Report of Four Cases
Authors: Kirk D. Miller
Journal: Annals of Internal Medicine (2000)

Background: An association between use of zidovudine and didanosine and a rare but life-threatening syndrome of hepatic steatosis, lactic acidosis, and myopathy has been reported. Objective: To describe the syndrome of hepatic steatosis, lactic acidosis, and myopathy in four patients taking stavudine. Design: Case series. Setting: A community hospital in Washington, D.C., and National Institutes of Health Clinical Center, Bethesda, Maryland. Patients: Two men and two women with HIV-1 infection who were taking stavudine presented with lactic acidosis and elevated levels of aminotransferases. All patients required intensive care. Measurements: Levels of lactic acid, alanine aminotransferase, aspartate aminotransferase, amylase, and lipase; computed tomography of the abdomen; liver biopsy (two patients); and muscle biopsy (two patients). Results: Histologic findings consistent with mitochondrial injury confirmed the diagnosis of hepatic or muscle abnormality. Conclusion: Because hepatic steatosis may be life-threatening, physicians should consider it as a possible cause of elevated hepatic aminotransferase levels among patients taking stavudine.
Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis
Authors: Daniel J. Anderson, Ronan Le Moigne, Stevan Djakovic, Brajesh Kumar, Julie Rice, Steve Wong, Jinhai Wang, Bing Yao, Eduardo Valle, Szerenke Kiss von Soly, Antonett Madriaga, Ferdie Soriano, Mary-Kamala Menon, Zhi Yong Wu, Martin Kampmann, Yuwen Chen, Jonathan S. Weissman, Blake T. Aftab, F. Michael Yakes, Laura Shawver, Han-Jie Zhou, David Wustrow, Mark Rolfe
Journal: Cancer Cell (2015)
<i>D<scp>rosophila</scp></i>: The Genetics of Innate Immune Recognition and Response
Authors: Catherine A. Brennan, Kathryn V. Anderson
Journal: Annual Review of Immunology (2004)

Because of the evolutionary conservation of innate mechanisms of host defense, Drosophila has emerged as an ideal animal in which to study the genetic control of immune recognition and responses. The discovery that the Toll pathway is required for defense against fungal infection in Drosophila was pivotal in studies of both mammalian and Drosophila immunity. Subsequent genetic screens in Drosophila to isolate additional mutants unable to induce humoral responses to infection have identified and ordered the function of components of two signaling cascades, the Toll and Imd pathways, that activate responses to infection. Drosophila blood cells also contribute to host defense through phagocytosis and signaling, and may carry out a form of self-nonself recognition that is independent of microbial pattern recognition. Recent work suggests that Drosophila will be a useful model for dissecting virulence mechanisms of several medically important pathogens.