tbuckley/cabot-search huggingface dataset:
Endothelial Cells Overexpressing Interleukin-8 Receptors Reduce Inflammatory and Neointimal Responses to Arterial Injury
Authors: Dongqi Xing, Peng Li, Kaizheng Gong, Zhengqin Yang, Hao Yu, Fadi G. Hage, Suzanne Oparil, Yiu-Fai Chen
Journal: Circulation (2012)

Background— Interleukin-8 (IL8) receptors IL8RA and IL8RB on neutrophil membranes bind to IL8 and direct neutrophil recruitment to sites of inflammation, including acutely injured arteries. This study tested whether administration of IL8RA- and/or IL8RB-transduced rat aortic endothelial cells (ECs) accelerates adhesion of ECs to the injured surface, thus suppressing inflammation and neointima formation in balloon-injured rat carotid arteries. We tested the hypothesis that targeted delivery of ECs by overexpressing IL8RA and IL8RB receptors prevents inflammatory responses and promotes structural recovery of arteries after endoluminal injury. Methods and Results— Young adult male rats received balloon injury of the right carotid artery and were transfused intravenously with ECs (total, 1.5×10 6 cells at 1, 3, and 5 hours after injury) transduced with adenoviral vectors carrying IL8RA, IL8RB, and IL8RA/RB (dual transduction) genes, AdNull (empty vector), or vehicle (no EC transfusion). ECs overexpressing IL8Rs inhibited proinflammatory mediators expression significantly (by 60% to 85%) and reduced infiltration of neutrophils and monocytes/macrophages into injured arteries at 1 day after injury, as well as stimulating a 2-fold increase in reendothelialization at 14 days after injury. IL8RA-EC, IL8RB-EC, and IL8RA/RB-EC treatment reduced neointima formation dramatically (by 80%, 74%, and 95%) at 28 days after injury. Conclusions— ECs with overexpression of IL8RA and/or IL8RB mimic the behavior of neutrophils that target and adhere to injured tissues, preventing inflammation and neointima formation. Targeted delivery of ECs to arteries with endoluminal injury provides a novel strategy for the prevention and treatment of cardiovascular disease.
Squamous Cell Carcinoma of the Skin in Adolescence
Authors: Robert A. Harvey
Journal: JAMA (1977)

IN SPITE OF its frequent occurrence in adults, squamous cell carcinoma of the skin is very rare in children. A computer search of the literature shows that only two cases of this disease have been reported in adolescents. We report a third case. <h3>Report of a Case</h3> A 14-year-old boy was referred to Memorial Hospital for Cancer and Allied Diseases for evaluation of a lesion over the bridge of the nose. This was first noted by the patient three months prior to admission as a persistent area of erythema with induration. Two weeks prior to admission this was excised, and the defect was closed primarily. Pathologic evaluation was said to disclose an infiltrating squamous cell carcinoma, and slides submitted to Memorial Hospital confirmed this diagnosis. The patient had been six weeks premature at birth. During his first week of life, spontaneous bilateral pneumothoraxes developed; these were treated with chest intubation.
An Alternative to the Double Blind Procedure
Authors: WILLIAM GUY, MARTIN GROSS, HELEN DENNIS
Journal: American Journal of Psychiatry (1967)

Therapists' bias may influence the assessment of treatment results even when the procedure purports to be a blind one. The authors advocate the employment of an independent assessment team (IAT) as an alternative to the classical double blind technique. They feel the IAT serves as an additional control over therapist bias and permits the use of modified double blind procedures in a variety of research situations.
Chronic hypertension during pregnancy
Authors: T. D. Clausen, T. Bergholt
Journal: BMJ (2014)

A growing problem that deserves more attention

Hypertensive disorders of pregnancy are among the leading causes of fetal and maternal morbidity and mortality. Worldwide, 50 000 to 60 000 women die from pre-eclampsia each year, corresponding to 12% of all maternal deaths.1 2

Pre-gestational hypertension has traditionally been considered a benign and stable condition in pregnant women and has attracted little attention from researchers. A linked systematic review and meta-analysis on chronic hypertension during pregnancy by Bramham and colleagues (doi:10.1136/bmj.g2301) seriously questions this perception and underlines the need for a much more explicit concern.3 The review included 55 studies on chronic hypertension during pregnancy, comprising both observational cohort studies and data from interventional trials from 25 different countries. The authors compared data from studies based on US cohorts with general population incidence obtained from the US National Vital Statistics Report (2006).

Hypertension in pregnancy is usually defined as a blood pressure of 140/90 mm Hg or above and proteinuria as a daily protein excretion of 300 mg or above, a protein:creatinine ratio of 0.3 or above, or 1+ on a urine dipstick.1 However, definitions are inconsistent …
Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling
Authors: Jennie L Conroy, Cheng Fang, Jun Gu, Scott O Zeitlin, Weizhu Yang, Jun Yang, Melissa A VanAlstine, Julia W Nalwalk, Phillip J Albrecht, Joseph E Mazurkiewicz, Abigail Snyder-Keller, Zhixing Shan, Shao-Zhong Zhang, Mark P Wentland, Melissa Behr, Brian I Knapp, Jean M Bidlack, Obbe P Zuiderveld, Rob Leurs, Xinxin Ding, Lindsay B Hough
Journal: Nature Neuroscience (2010)
Is there a future for links pages?
Authors: Douglas Carnall
Journal: BMJ (2004)

It has been almost 10 years since the internet exploded into common use. Those who were going to learn html and install servers have done so, institutions have found their internet policies and are sticking to them, and users have settled down into comfortable patterns of behaviour. The internet is no longer “hot”: like plumbing, we'll certainly miss it if it's not there, but the grand visions of those heady days seem wrecked on the rocks of institutions just continuing to do what they have always done.

In the mid-1990s, when search engines' …
Diesel Exposure Favors Th2 Cell Recruitment by Mononuclear Cells from Nonatopic Subjects by Differentially Regulating CCL18/PARC and CXCL10/IP-10 Production
Authors: Y. Chang, S. Senechal, P. de Nadai, C. Chenivesse, J. Gilet, H. Vorng, A. Tonnel, B. Wallaert, A. Tsicopoulos
Journal: Journal of Allergy and Clinical Immunology (2006)
Correction of hyponatraemia in cirrhosis: Treating more than a number!
Authors: Andrés Cárdenas, Oliviero Riggio
Journal: Journal of Hepatology (2014)

Patients with advanced cirrhosis and ascites or oedema cannot only avidly retain sodium but also solute-free water due to renal abnormalities that occur in the natural course of the disease. With time, solute-free water retention leads to a dilutional or hypervolemic state where water is retained in excess of sodium, causing hyponatraemia, and hypoosmolality [1]. The main pathogenic factor responsible for hyponatraemia in this setting is a non-osmotic hypersecretion of arginine vasopressin (AVP, or antidiuretic hormone) from the neurohypophysis related to circulatory dysfunction.
Immunoglobulin heavy chain variable region family expression in primary cutaneous follicle centre cell lymphomas
Authors: M. Alaibac, A. Belloni-Fortina, M. Mori, B. Pigozzi, A. Peserico, N. Pimpinelli
Journal: British Journal of Dermatology (2001)

Primary cutaneous follicle centre cell lymphomas (PCFCCL) are the most common type of primary cutaneous B-cell lymphomas. Patients with this disorder develop one or a few clinically indolent tumour nodules, plaques, or papules confined to a circumscribed area. Only limited data have so far been published on the use of immunoglobulin heavy chain variable region (VH) families by these tumours.Because the definition of the repertoire of VH genes could have significant biological and diagnostic implications, we evaluated a group of patients with PCFCCL for VH family use.DNA obtained from 15 cases of PCFCCL was amplified by polymerase chain reaction (PCR) using a panel of VH family-specific amplimers.The pattern of VH family usage was similar to that reported in both normal peripheral blood B cells and the most common low grade non-Hodgkin's lymphomas, where VH region utilization is essentially random with frequent usage of the VH3 family.These findings support the hypothesis that PCFCCL may derive from the mature peripheral lymphoid compartment. Our results may also have implications for the routine analysis of B-lymphoid clonality in PCFCCL.
The Napkin-Ring Sign: CT Signature of High-Risk Coronary Plaques?
Authors: Pál Maurovich-Horvat, Udo Hoffmann, Marc Vorpahl, Masataka Nakano, Renu Virmani, Hatem Alkadhi
Journal: JACC. Cardiovascular imaging (2010)

histopathology has demonstrated that rupture of coronary atherosclerotic plaques with subsequent intraluminal formation of thrombi is the most frequent cause of acute myocardial infarction ([1][1]).

Furthermore, it has been shown that plaque ruptures resemble plaques that are histologically
<scp>D</scp>-Penicillamine Therapy in Progressive Systemic Sclerosis (Scleroderma)
Authors: VIRGINIA D. STEEN
Journal: Annals of Internal Medicine (1982)

In a retrospective study on progressive systemic sclerosis, we compared 73 patients who had received D-penicillamine therapy for a minimum of 6 consecutive months with 45 patients who had not received this drug. All patients had diffuse sclerodermatous skin changes and early disease (less than 3-years duration). D-Penicillamine was prescribed for an average of 24 months (range, 6 to 68 months) with a maximum daily dose of 500 to 1500 mg (median, 750 mg). During a mean follow-up interval of 38 months, the degree and extent of skin thickness, determined on physical examination, decreased considerably more in the patients treated with D-penicillamine than in patients in the comparison group (p = 0.07). The rate of new visceral organ involvement was reduced in patients treated with D-penicillamine, especially for the kidney (p = 0.01). Patients treated with D-penicillamine had a greater 5-year cumulative survival rate (88% versus 66%, p < 0.05). Therapy with colchicine (23 patients) or immunosuppressive agents (26 patients) was not associated with these improvements.
Seven-Year "Cure" of Lung Cancer With Metastasis to the Brain
Authors: G. L. Hendricks
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Pulmonary resection is considered to be contraindicated in patients with carcinoma of the lung who have cerebral metastases.<sup>1</sup>Recommendations for proper therapy of a solitary cerebral metastasis vary widely. Knight thought that both the primary and secondary growths should be excised, and found a definite prolongation of the patient's life thereby.<sup>2</sup>Others<sup>3-6</sup>also indicated that if the metastatic lesion is single and located in an accessible part of the brain, extirpation may result in a longer survival time, with relief of many distressing and disabling symptoms. Flavell reported a patient who was alive, well, and working ten years after resection of both the pulmonary tumor and the cerebral metastasis.<sup>7</sup>Bakay reported five-year survival after resection of an intracranial metastasis followed by radiation therapy to the primary lesion.<sup>8</sup>At autopsy, a huge brain cyst was found, but there was no residual tumor in
END-RESULTS OF RADIUM REMOVAL OF CARCINOMA OF THE BLADDER
Authors: B. S. BARRINGER
Journal: JAMA (1928)

To determine the value of radium removal of carcinoma of the bladder, I have tabulated the end-results in cases in which five years had elapsed since irradiation; in other words, I am reporting all cases treated up to the end of 1922. Only cases in which the carcinoma arose from the epithelial layer are listed. These are divided as accurately as possible into cases of papillary and of infiltrating carcinoma. In both the papillary and infiltrating types, some cases have been included in which a pathologic examination was not made or in which the pathologic examination did not, to my mind, reveal the real diagnosis. In the papillary group, if the diagnosis of a small piece of the tumor showed simple papilloma, and if the tumor was sloughy in whole or in part, or did not disappear after the performance of repeated and intelligent fulgurations, that tumor was classified as
Abstract 5562: Generation and characterization of highly selective cathepsin S inhibitors with potentials against pancreatic cancer.
Authors: Wun-Shaing W. Chang, Chien-Yu Liao, Yi-Hsun Chang, Tzu Chin Wu, Rou-Jhen Wu, Tien-Ning Chang, Jang-Yang Chang, Chun-Cheng Lin
Journal: Cancer Research (2013)

Abstract Cathepsin S (CTSS) is a critical cellular protease required for cancer development and metastasis. This proteolytic enzyme is often over-expressed by malignant tumor cells and secreted into the extracellular milieu to degrade surrounding matrix components. Here, we attempted to systematically generate and evaluate potential CTSS inhibitors in hope to identify potent candidates for use as antitumor agents. Detailed kinetic analysis revealed several lead compounds possess very low Ki values and high specificity against target CTSS protease. Results from ECM degradation assays demonstrated that these small molecules could protect fibronectin from CTSS-mediated degradation and consequently hinder tumor cell movement. Treating various pancreatic tumor cell lines with these CTSS inhibitors further resulted in a drastic decrease in cell migration and invasion. The test compounds also reduced the spread of pancreatic tumor cells in orthotopic animal model and thus prolonged mice survival. Finally, these lead molecules exhibited reasonable pharmacokinetic (PK) profiles, suggesting their potential as antitumor agents against pancreatic cancer. Citation Format: Wun-Shaing W. Chang, Chien-Yu Liao, Yi-Hsun Chang, Tzu Chin Wu, Rou-Jhen Wu, Tien-Ning Chang, Jang-Yang Chang, Chun-Cheng Lin. Generation and characterization of highly selective cathepsin S inhibitors with potentials against pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5562. doi:10.1158/1538-7445.AM2013-5562
Afghanistan: a biased report
Authors: A O Gebreel
Journal: BMJ (1997)

<h3>Abstract</h3> Many cell surface stimuli cause calcium release from endoplasmic reticulum (ER) stores to regulate cellular physiology. Upon ER calcium store depletion, the ER-resident protein STIM1 physically interacts with plasma membrane protein Orai1 to induce calcium release-activated calcium (CRAC) currents that conduct calcium influx from the extracellular milieu. Although the physiological relevance of this process is well established, the mechanism supporting the assembly of these proteins is incompletely understood. Earlier we demonstrated a previously unknown post-translational modification of Orai1 with long chain fatty acids, known as S-acylation. We found that S-acylation of Orai1 is dynamically regulated in a stimulus-dependent manner and essential for its function as a calcium channel. Here we show that STIM1 is also rapidly and transiently S-acylated at cysteine 437 upon ER calcium store depletion. S-acylation of STIM1 is required for the assembly of STIM1 into puncta with Orai1 and full CRAC channel function. Together with the S-acylation of Orai1, our data suggest that stimulus-dependent S-acylation of CRAC channel components Orai1 and STIM1 is a critical mechanism facilitating CRAC channel assembly and function.
11 IMPACT OF IL28B GENOTYPE AND PRETREATMENT SERUM IP-10 IN TREATMENT-NAIVE GENOTYPE-1 HCV PATIENTS TREATED WITH TMC435 IN COMBINATION WITH PEGINTERFERONa-2A AND RIBAVIRIN IN PILLAR STUDY
Authors: J. Aerssens, G. Fanning, A. Scholliers, O. Lenz, M. Peeters, G. De Srnedt, M. Fried
Journal: Journal of Hepatology (2011)
Evidence for a Role of the Microtubular System in the Secretion of Newly Synthesized Albumin and Other Proteins by the Liver
Authors: Yannick Le Marchand, Christoph Patzelt, Françoise Assimacopoulos-Jeannet, Ernest G. Loten, Bernard Jeanrenaud
Journal: Journal of Clinical Investigation (1974)

Livers of normal mice were prefused in situ and the secretion of newly synthesized (i.e. labeled) proteins into the perfusate were measured. In control livers, the secretion of newly synthesized proteins was found to be linear with time. In marked contrast, when livers were perfused with vinblastine, vincristine, or colchicine, drugs known to interfere with the hepatic microtubular system, the release of newly synthesized proteins was either strongly inhibited or completely suppressed although total hepatic protein synthesis (estimated by the incorporation of labeled amino acids into hepatic plus perfusate proteins) remained unaltered. Chromatographic separation of the various secreted proteins showed that the release of albumin, globulins, and small polypeptides was decreased to a similar extent by vincristine or colchicine. In the particular case of albumin, it was further observed that total (i.e. liver plus perfusate) labeled amino acid incorporation into albumin was not altered by either vincristine or colchicine, whereas the incorporation of these amino acids into liver albumin was markedly increased but incorporation into perfusate albumin was decreased, suggesting that the translocation of this particular protein from the liver to the perfusate had been affected by the presence of these drugs. It is proposed that the functional integrity of microtubules is necessary for the intracellular movement and eventual release of albumin and other proteins by the liver, and suggested that microtubules might possibly be a site of regulation of hepatic protein secretion.
Dissemination of Tubercle Bacilli.
Authors: J. J. Curry
Journal: JAMA (1899)

Savannah, Ga., April 20, 1899. <h3>To the Editor:</h3> —Referring to the editorial in theJournalof April 15 (p. 827), I think Flügge greatly exaggerates the danger of infection by means of the fine drops expelled from the mouths of phthisic persons in coughing. He has<i>not</i>by any means proved that tuberculosis is<i>commonly</i>transmitted by such drops. I believe the only danger, save in exceptional cases, of the open mouth coughing, is that such drops soon become dried and act as so much dried sputum. The danger of inhaling such drops under ordinary circumstances is slight. Cornet's recent works proved conclusively that tuberculosis may be disseminated by dried sputum dust. Very respectfully,
Scrap the royal colleges' fellowships
Authors: Des Spence
Journal: BMJ (2013)

We are all a product of our time, a morass of contradictions, conflicts, and prejudices. I was raised on a isolated Scottish island, attended a comprehensive school, and worked in many different jobs. I pride myself on my ordinariness and the ordinariness of my medical work. Egalitarianism is branded in my psyche. I am intent on never appearing intimidated—even when I am. I am respectful but not deferential. I dislike titles, including “Doctor,” reasoning that these are merely a weapon of intimidation. Success and …
Endoscopical Follow-up Observation of Duodenal Ulcer
Authors: Y. Kohli, F. Misaki, K. Kawai
Journal: Endoscopy (1972)

1. From the endoscopical follow-up study of the 66 cases of duodenal ulcers, we found the round or irregularly shaped duodenal ulcer changed itself into linear, irregular, or “Salami” in shape. — 2. “Salami” type of duodenal ulcer was seen in the healing or recurring process of the round or irregularly shaped ulcer. — 3. The linear ulcer was unchanged in its shape and its healing tendency was too low, compared with another type of duodenal ulcer. From these clinical results, we concluded the linear ulcer was considered to be the final stage of duodenal ulcer like gastric ulcer. — 4. From the histological examination of the biopsied or surgically resected materials of “Salami” type, it was proved to be an erosion, arising from the round or irregularly shaped duodenal ulcer, or in the immature mucosa of the scar formation, or in the normal duodenal mucosa. — 5. In each shape of duodenal ulcer, its healing tendency was investigated. Single round ulcer is easy to heal, and the linear one is most intractable. The healing ratio of round ulcer was estimated to be about 60% in a month after the first endoscopic observation, and its mean healing time was about 26 days.
Thousands face compulsory treatment in the community under new UK act
Authors: Sophie Arie
Journal: BMJ (2005)

The number of community based patients treated compulsorily under the proposed new mental health legislation could be close to 10 times higher than the government expects, a report by the King's Fund has said.

If the controversial Mental Health Bill 2004 becomes law, in the first 10 to 15 years between 7800 and 13 000 people could be subject to compulsory orders, the medical think tank said.

The Department of Health dismissed the report saying that the “lack of quality data and weakness in analysis” meant that the estimates were “flawed” and failed to …
Lactagol—To Promote Lactation.
Authors: None Lehn & Fink
Journal: JAMA (1904)

New York City, April 12, 1904. <h3>To the Editor:</h3> —InThe Journal, March 12, in the department of "Current Medical Literature," there is an abstract from an article in the<i>Berliner klinische Wochenschrift</i>on lactagol [page 744, abstract 80]. In reference thereto we call your attention to the fact that you make it appear that lactagol is a powdered product of cottonseed. We are just in receipt of a communication from Messrs. Pearson &amp; Co. of Hamburg, the manufacturers of the preparation, in which we are requested to inform you that the preparation is an extract of cottonseed and not the cottonseed itself.
GE-19 * GENOMICS GUIDED THERAPEUTIC APPROACH FOR THE TREATMENT OF GLIOBLASTOMA MULTIFORME (GBM) USING NEXT GENERATION SEQUENCING (NGS) TECHNOLOGIES
Authors: D. Ma, J. Sarkaria, S. Peng, S. Byron, D. Craig, J. Carpten, M. Berens, B. O'Neill, M. Schroeder, N. Tran
Journal: Neuro-Oncology (2014)

BACKGROUND: The genomic heterogeneity of glioblastoma likely underlies the low response rates (8-24%) for targeted agents among unselected populations. We tested whether NGS would be useful in identifying therapeutically-actionable genetic alterations; we sought to test if this translated into improved tumor control in a patient-derived GBM model. METHODS: Tumor specimens from each patient (n = 11) that were used for analyte extraction contained between 70-80% viable tumor cellularity. Genome sequence coverage was more than 30X for both tumor and germline genomes; tumor RNA sequencing included over 100 million reads. NGS of paired tumor and germline DNA enabled detection of single nucleotide variations (SNVs), indels, translocations, intra-chromosomal rearrangements, and copy number alterations. A custom drug-matching workflow utilizing publically available databases and curated literature on reported drug effects, pharmacokinetics, and blood-brain barrier (BBB) penetration was used to map individual gene alterations in tumors with associated drug-response relationships. One specimen was tested in vitro and in vivo using a matched, patient-derived xenograft model. RESULTS: NGS for the 11 tumor panel found ∼30% of cases with EGFR amplification, p16, and/or PTEN deletion. Novel potentially actionable targets included a TRIM54-FGFR3 fusion, STAG2 mutation, KIF11 and KIF15 mutation, and BRAF amplification. One recurrent, MGMT-unmethylated GBM line with a TRIM54-FGFR3 fusion underwent chemovulnerability testing. Cyquant proliferation assays demonstrated sensitivity to the pan-FGFR1-3 inhibitor AZD4547 when compared to a line without FGFR alteration (IC50 3uM vs >10uM). Furthermore, a flank PDX study demonstrated significant activity by AZD4547 when compared with either placebo or temozolomide, resulting in near complete tumor stasis at 82+ days of dosing with AZD4547. CONCLUSIONS: These results support the notion that therapeutic planning for treatment of GBM can be individualized and predicted by genome- and transcription-based analysis on the primary tumor, with the ultimate goal to design individualized GBM therapy based upon genetic markers for treatment sensitivity.