tbuckley/cabot-search huggingface dataset:
The isolation and characterization of a Norwalk virus-specific cDNA.
Authors: S M Matsui, J P Kim, H B Greenberg, W Su, Q Sun, P C Johnson, H L DuPont, L S Oshiro, G R Reyes
Journal: Journal of Clinical Investigation (1991)

Norwalk virus, an important cause of epidemic, acute, nonbacterial gastroenteritis in adults and children, has eluded adaptation to tissue culture, the development of an animal model, and molecular cloning. In this study, a portion of the Norwalk viral genome encoding an immunoreactive region was cloned from very small quantities of infected stool using sequence-independent single primer amplification. Six overlapping complementary DNA (cDNA) clones were isolated by immunologic screening. The expressed recombinant protein from a representative clone reacted with six of seven high titer. Norwalk-specific, postinfection sera but not with corresponding preinfection sera. Nucleic acid sequence for all clones defined a single open reading frame contiguous with the lambda gt11-expressed beta-galactosidase protein. Only oligonucleotide probes specific for the positive strand (defined by the open reading frame) hybridized to an RNaseA-sensitive, DNaseI-resistant nucleic acid sequence extracted from Norwalk-infected stool. Furthermore, RNA extracted from serial postinfection, but not preinfection, stools from three of five volunteers hybridized to a Norwalk virus cDNA probe. Clone-specific oligonucleotide probes hybridized with cesium chloride gradient fractions containing purified Norwalk virion. In conclusion, an antigenic, protein-coding region of the Norwalk virus genome has been identified. This epitope has potential utility in future sero- and molecular epidemiologic studies of Norwalk viral gastroenteritis.
Identifying asthma and chronic obstructive pulmonary disease in patients with persistent cough
Authors: J. M Rothenberg, A B Chang, I B Masters, H A Thiadens, D S Postma
Journal: BMJ (1998)

# Why was no control group studied? {#article-title-2} EDITOR —Thiadens et al examined 192 patients presenting to their general practitioner with persistent cough —a common and challenging problem in primary care —and found a high prevalence of asthma (39%) and chronic obstructive pulmonary disease (7%).1 I was disappointed that they did not provide a control group of asymptomatic subjects in the community. What is the prevalence of abnormal results of pulmonary function tests in their general population? If it is high, with a prevalence approaching the prevalence found in their population of patients with cough, an alternative conclusion might be that asthma and chronic obstructive pulmonary disease are common and not significantly more common in the population of patients with cough. I encourage Thiadens et al to examine their study group further. One issue deserving scrutiny is whether these patients are still coughing after six months. Also, what diagnoses (if any) apply to the remaining (54%) patients with cough, and does their prognosis differ from that of the group diagnosed as having asthma and chronic obstructive pulmonary disease? Finally, how do these patients respond to different treatments? 1. ↵1. Thiadens HA, 2. de Bock GH, 3. Dekker FW, 4. Huysman JAN, 5. van H, 6. ouwelingen JC, 7. Springer MP, 8. et al. Identifying asthma and chronic obstructive pulmonary disease in patients with persistent cough presenting to general practitioners: descriptive study.BMJ1998; 316:1286–1290. (25 April.) [OpenUrl][1][Abstract/FREE Full Text][2] # Children with cough alone should not be labelled asthmatic {#article-title-4} EDITOR —Thiadens et al devised a score to estimate the probability of asthma or chronic obstructive pulmonary disease in patients who present … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DThiadens%26rft.auinit1%253DH%2BA%26rft.volume%253D316%26rft.issue%253D7140%26rft.spage%253D1286%26rft.epage%253D1290%26rft.atitle%253DIdentifying%2Basthma%2Band%2Bchronic%2Bobstructive%2Bpulmonary%2Bdisease%2Bin%2Bpatients%2Bwith%2Bpersistent%2Bcough%2Bpresenting%2Bto%2Bgeneral%2Bpractitioners%253A%2Bdescriptive%2Bstudy%26rft_id%253Dinfo%253Apmid%252F9554899%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bmj&resid=316/7140/1286&atom=%2Fbmj%2F317%2F7165%2F1078.2.atom
51 Optimal virologic and clinical efficacy at one year is associated with maximal early HBV suppression in nucleoside-treated hepatitis B patients
Authors: S. Zeuzem, C.L. Lai, E. Gane, Y.F. Liaw, S. Thongsawat, Y. Wang, Y. Chen, J. Heathcote, J. Rasenack, N. Bzowej, N. Naoumov, G. Chao, B. Fielman, N. Brown
Journal: Journal of Hepatology (2006)
Tumor Lysis Syndrome After Capecitabine Plus Cisplatin Treatment in Advanced Gastric Cancer
Authors: Hye-Suk Han, Sook Ryun Park, Sun Young Kim, Young Iee Park, Jong Seok Lee, Myeong-Cherl Kook, Il Ju Choi, Chan Gyoo Kim, Jong Reul Lee, Soo Jeong Cho, Noe Kyeong Kim
Journal: Journal of Clinical Oncology (2008)
Yield of Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Bile Duct Lesions
Authors: M. F. Byrne, H. Gerke, R. M. Mitchell, H. L. Stiffler, K. McGrath, M. S. Branch, J. Baillie, P. S. Jowell
Journal: Endoscopy (2004)

It is still difficult to differentiate reliably between benign and malignant biliary tract lesions. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has added to the diagnostic power of EUS for other gastrointestinal tumors. A retrospective analysis of experience with FNA sampling of bile duct lesions was therefore carried out.All EUS-FNA procedures for bile duct masses or strictures were analyzed at our tertiary referral center from May 2000 through October 2002. Data for EUS findings, the results of EUS-FNA, and tissue sampling at surgery were included. EUS-FNA procedures were carried out using a 22-gauge needle. An experienced cytopathologist was present during FNA in all but three cases. Clinical follow-up details were recorded when available for patients in whom a suitable diagnostic gold standard was not available for comparison.A total of 35 patients underwent EUS-FNA of bile duct lesions during the study period. There were no complications. Data for EUS-FNA of bile duct masses or strictures and tissue obtained at surgery were available for 23 patients. If positive cytology at surgical pathology is taken as the gold standard, EUS-FNA has a diagnostic yield for cancer of 100 % (if atypia/inconclusive findings in the FNA sample are regarded as benign). Eleven patients had a definite malignancy on surgical pathology. Of these 11 patients, five had a finding of malignancy on EUS-FNA, giving a sensitivity of 45 % (if FNA cytology reported as atypia/inconclusive is regarded as benign). Twelve patients had findings of no malignancy from tissue obtained at surgery. Of these 12 patients, nine had benign pathology and three had atypia/inconclusive findings in the EUS-FNA sample (specificity of 100 % if atypia/inconclusive findings are considered benign). A further 12 patients did not have surgical specimens for comparison with EUS-FNA results. Four patients had definite findings of malignancy on EUS-FNA alone, and one patient had FNA findings suspicious for malignancy. Seven patients had negative or equivocal EUS-FNA results. These 12 patients are described but excluded from further analysis, as a gold standard was not available for comparison. However, clinical follow-up data were available for eight of these 12 patients, and in each case the follow-up findings were compatible with previous benign or malignant EUS-FNA findings.The practice of EUS-FNA has improved the diagnostic yield of EUS. These results suggest that it is a safe and useful procedure for investigating biliary masses or strictures that have hitherto caused considerable diagnostic confusion, especially in patients with negative brush cytology findings. The possibility of false-negative findings remains, but core biopsy needles may improve the situation. The results of further studies are awaited.
Screening without evidence of efficacy
Authors: Birte Twisselmann
Journal: BMJ (2004)

EDITOR—Law's editorial on screening without evidence of efficacy prompted a predictably substantial number of responses that were, perhaps not so predictably, mostly united in their agreement with his objections to advocating screening of unproved value.1 He concludes: “For a new drug a rigorous set of experimental data must be presented before it is licensed for use, and until it is licensed patients cannot obtain it. The same rigour should apply to medical screening.”

Most of the responses questioned the value of screening and …
Postoperative Clostridial Infections in Britain
Authors: M. T. Parker
Journal: BMJ (1969)

Eighty-five cases of clostridial infection, including 56 cases of gas gangrene, followed "clean" surgical operations performed in British hospitals in the course of two years. Nearly all the serious infections followed amputations of the leg for ischaemia or other operations on the leg in which a foreign body was implanted. All the infections were sporadic, and the evidence suggested that the infecting organism usually came from the bowel of the patient. Nearly half of the operations were performed in modern theatres with satisfactory ventilation and unexceptionable arrangements for the sterilization of instruments and dressings.Skin sterilization was often carried out perfunctorily or with agents with poor sporicidal activity. Total eradication of spores from the skin is, however, difficult to achieve, and recontamination may occur during the operation. Hence it is considered justifiable to give penicillin prophylactically to the small group of patients at serious risk from postoperative gas gangrene.
Development, characterisation and optimisation of poly(methylmethacrylate) bone cement formulations for appli-cation as a space maintainer in a staged strategy for cranio-facial bone regeneration
Authors: Fionnuala M. Hinds, Patrick Spicer, Meng Shi, Mark E. Wong, F. Kurtis Kasper, Antonios G. Mikos
Journal: International Journal of Surgery (2011)
Megakaryocyte DNA content is increased in patients with coronary artery atherosclerosis
Authors: P. M W Bath, A.-M. Gladwin, N. Carden, J. F Martin
Journal: Cardiovascular Research (1994)

Objective: Increased megakaryocyte size and megakaryocyte ploidy have been observed in man following myocardial infarction and sudden cardiac death. The aim of this study was to compare megakaryocyte ploidy in patients with and without coronary artery atherosclerosis. Methods: Sternal megakaryocytes were obtained immediately prior to cardiac surgery in 26 patients with significant coronary artery atherosclerosis requiring surgical bypass grafting and in 14 age matched control patients requiring cardiac valve replacement or repair with minimal or no coronary atherosclerosis on arteriography. Megakaryocytes were identified using a monoclonal antibody to the CD41 (GPIIb/IIIa) surface antigen and ploidy was studied using flow cytometry. Results: Megakaryocyte modal ploidy was significantly higher in the coronary atherosclerosis patients (modal ploidy 8N, n = 0 subjects; 16N, n = 16; 32N, n = 10) as compared with the control group (modal ploidy 8N, n = 5 subjects; 16N, n = 7; 32N, n = 2), p = 0.008. Ploidy correlated with the degree of coronary atherosclerosis defined as the number of atherosclerotic vessels observed on angiography (r = 0.51, p< 0.001, 95% confidence limits 0.25 to 0.70) and the serum total cholesterol concentration (r = 0.50, p = 0.006, 95% confidence limits 0.18 to 0.72). Bleeding time was not different [315(semiquartile range 45) s v 315(75) s] between the two groups in spite of the fact that 20 of 26 coronary atherosclerosis patients were taking aspirin versus one of 14 valve patients. Conclusions: Megakaryocyte ploidy is increased in human coronary atherosclerosis and correlates with serum lipids. Hypercholesterolaemia may induce increases in megakaryocyte ploidy, and hence the production of hyperfunctional platelets, which will contribute to atherogenesis. Cardiovascular Research 1994;28:1348-1352
<i>FLG</i>mutations in ichthyosis vulgaris and atopic eczema: spectrum of mutations and population genetics
Authors: M. Akiyama
Journal: British Journal of Dermatology (2009)

Filaggrin is a key protein involved in skin barrier function. Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris and have been shown to be major predisposing factors for atopic eczema (AE), initially in European populations. Subsequently, FLG mutations were identified in Japanese, Chinese, Taiwanese and Korean populations. It was demonstrated that FLG mutations are closely associated with AE in the Japanese population. Notably, the same FLG mutations identified in the European population were rarely found in Asians. These results exemplify differences in filaggrin population genetics between Europe and Asia. For mutation screening, background information needs to be obtained on prevalent FLG mutations for each geographical population. It is therefore important to establish the global population genetics maps for FLG mutations. Mutations at any site within FLG, even mutations in C‐terminal imperfect filaggrin repeats, cause significant reductions in amounts of profilaggrin/filaggrin peptide in patient epidermis as the C‐terminal region is essential for proper processing of profilaggrin into filaggrin. Thus, no genotype–phenotype correlation has been observed in patients with FLG mutations. A restoration of the barrier function seems a feasible and promising strategy for treatment and prevention in individuals with filaggrin deficiency.
Osseous Metaplasia in Soft Tissue
Authors: Russell C. Briggs
Journal: JAMA (1966)

RADIOISOTOPE scintiscanning for demonstration of osseous metastatic disease is now an accepted procedure. Abnormal scans can also be obtained in primary neoplasms of bone as well as in a number of benign conditions. Heterotopic ossification in the stroma of primary epithelial neoplasms is relatively uncommon.<sup>1</sup>The presence of bone formation in soft-tissue metastatic disease is a rare occurrence, and the demonstration of this change by scintiscanning is consequently a singular event. Heterotopic new bone in metastatic disease to the abdominal wall has been seen in three cases of intestinal adenocarcinoma<sup>1-3</sup>and in one case of carcinoma of the bladder.<sup>4</sup>Each of these instances may have represented surgical implantation of tumor cells rather than true hematogenous or lymphatic spread. However, heterotopic new bone was demonstrated both roentgenographically and histologically in a lymph node metastasis by Senturia et al<sup>5</sup>in one case of adenocarcinoma of the rectum. The
Leukotriene receptor antagonists in the treatment of asthma: an update
Authors: G. Balzano, S. Fuschillo, C. Gaudiosi
Journal: Allergy (2002)

Leukotriene receptor antagonists (LTRAs), such as montelukast and zafirlukast, have been demonstrated in a number of studies to possess bronchodilating and anti‐inflammatory properties, that make these drugs ideal candidates for the treatment of asthma. The last 1998‐updating of the GINA Guidelines for the diagnosis and therapy of asthma recommends the use of LTRAs in the treatment of moderate and mild asthma. In patients with moderate asthma not completely controlled with moderate doses of inhaled corticosteroids, the addition of a LTRA is indicated in alternative to either the increase of the inhaled corticosteroid dose or the addition of an inhaled long‐acting beta 2 ‐agonist. Both in vitro and in vivo evidences indicate that LTRAs possess an anti‐inflammatory activity that is presumably complementary to that presented by corticosteroids. Moreover, clinical studies show that the addition of an LTRA, montelukast, is able to improve clinical and functional indexes in patients with asthma not controlled with inhaled corticosteroids, and to allow a reduction in corticosteroid dosage in patients with asthma well controlled by inhaled corticosteroids. In patients with mild persistent asthma monotherapy with an LTRA is indicated in alternative to a low‐dose inhaled corticosteroid, an inhaled cromone, or an oral slow‐release theophylline. Previous clinical studies in patients with mild to moderate asthma had demonstrated that monotherapy with LTRAs is able to improve airway function, asthma symptoms, use of as‐needed medications, exacerbation rate, and quality of life, without evidence of tolerance with prolonged use. Recently, in a subgroup analysis of patients with mild persistent asthma, a 6‐week treatment with oral montelukast or inhaled beclomethasone gave similar improvements in ‘rescue‐free’ days, days with well controlled asthma, FEV 1 , blood eosinophils, beta‐agonist use, and nocturnal awakes due to asthma.
Metabolic inhibition of plaque-forming cells: comparison of human rheumatoid-factor-producing cells with mouse anti-sheep erythrocyte-producing cells.
Authors: T L Moore, J E Rose, J H Vaughan
Journal: Annals of the Rheumatic Diseases (1979)

While rheumatoid-factor-producing haemolytic plaque-forming cells (RF--PFC) of the human peripheral blood were easily inhibited by cycloheximide, mouse spleen cells immune to sheep red cells (anti-SRC PFC) were inhibited only after prolonged preincubation in the drug. The RF--PFC were easily inhibited by propranolol, while the anti-SRC PFC were not at all inhibited. Vinblastine inhibited both systems equally. These differences are taken to suggest that the RF--PFC have very little preformed antibody in them and therefore depend upon active protein synthesis for their demonstration. In contrast, anti-SRC PFC, which may be predominantly mature plasma cells, generally need no new protein synthesis for their demonstration because of increased quantities of preformed antibody. A possible mechanism is that RF--PFC may represent primarily RF-specific B cells, the RF of which is released by surface immunoglobulin shedding and therefore susceptible to membrane stabilising agents such as propranolol.
THE SERUM TREATMENT OF TYPHOID FEVER
Authors: R. C. Robertson, H. Yu
Journal: BMJ (1936)

FEVER-~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~EIA local anaesthesia.The administration of saline solution was continued by slow continuous drip.A portion of gangrenous ileum was found in the sac of a femoral hernia.This was resected but no anastomosis was attempted, rubber tubes being fixed into the ends of the divided bowel.When the proximal enterostomy was draining freely it was joined to the distal tube, but it was found that the proximal ileum was unable to empty itself into the distal portion of bowel via the tube.Ordinary gravity drainage was therefore re- established, but the contents were collected and utilized as in Case I.The patient's condition rapidly improved, and he was well on the way to recovery when, on the third day, he developed an acute chest lesion, from which he died.This case supports the experimental findings relating to strangulation of short segments of bowel within hernial sacs.The blood loss is small in amount, and toxins escaping into the closed hernial sac are but slowly absorbed.The main factor in this case was the result of the mechanical obstruction with dehydration and alkalosis causing severe tctany, which was rapidly relieved by intravenous saline.Summary 1.The method of exteriorization of strangulated bowel in patients who are gravely ill is one which can be carried out quickly and with a minimum of shock.2. Drainage of the bowel must be established, but excision of the affected segment may, if necessary, be left until twenty-four hours have elapsed.3. When a patient is seriously ill immediate resection and anastomosis increase the risks of pcritoneal infection and of rec-errent obstruction, since the over-distended proximal bowel may be unable to pass its contents through the new stoma.4. Operative procedures must be preceded by blood transfusion or intravenous saline infusions according to th3 type of intestinal obstruction to be dealt with.
Patched2 Modulates Tumorigenesis in Patched1 Heterozygous Mice
Authors: Youngsoo Lee, Heather L. Miller, Helen R. Russell, Kelli Boyd, Tom Curran, Peter J. McKinnon
Journal: Cancer Research (2006)

Abstract The sonic hedgehog (SHH) receptor Patched 1 (Ptch1) is critical for embryonic development, and its loss is linked to tumorigenesis. Germ line inactivation of one copy of Ptch1 predisposes to basal cell carcinoma and medulloblastoma in mouse and man. In many cases, medulloblastoma arising from perturbations of Ptch1 function leads to a concomitant up-regulation of a highly similar gene, Patched2 (Ptch2). As increased expression of Ptch2 is associated with medulloblastoma and other tumors, we investigated the role of Ptch2 in tumor suppression by generating Ptch2-deficient mice. In striking contrast to Ptch1−/− mice, Ptch2−/− animals were born alive and showed no obvious defects and were not cancer prone. However, loss of Ptch2 markedly affected tumor formation in combination with Ptch1 haploinsufficiency. Ptch1+/−Ptch2−/− and Ptch1+/−Ptch2+/− animals showed a higher incidence of tumors and a broader spectrum of tumor types compared with Ptch1+/− animals. Therefore, Ptch2 modulates tumorigenesis associated with Ptch1 haploinsufficiency. (Cancer Res 2006; 66(14): 6964-71)
Homocysteine Mediated Expression and Secretion of Monocyte Chemoattractant Protein-1 and Interleukin-8 in Human Monocytes
Authors: Xiaokun Zeng, Jing Dai, Daniel G. Remick, Xian Wang
Journal: Circulation Research (2003)

Homocysteine (Hcy) is an independent risk factor for cardiovascular disease. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) are major chemokines for leukocyte trafficking and have been identified in atheromatous plaques. MCP-1 and IL-8 have been found to express mainly by macrophages in human lesion. We undertook this study to determine whether Hcy could induce the secretion of chemokines from human monocytes and, if so, to explore the mediating mechanism. We found that clinically relevant levels of Hcy (10 to 1000 micromol/L) increased the protein secretion and mRNA expression as well as activity of MCP-1 and IL-8 in cultured primary human monocytes. These effects of Hcy were primarily mediated by reactive oxygen species (ROS) through NAD(P)H oxidase, because Hcy could upregulate the production of ROS and the inhibitors of protein kinase C, calmodulin, free radical scavengers, or NAD(P)H oxidase abolished Hcy-induced ROS production and MCP-1 and IL-8 secretion in these cells. Furthermore, the inhibitors of mitogen-activated protein kinase (p38 and extracellular signal-regulated kinase 1/2) and nuclear factor-kappaB or the activator of peroxisome proliferator-activated receptor gamma (PPARgamma) significantly decreased Hcy-induced MCP-1 and IL-8 secretion in these cells. These data indicate that pathophysiological levels of Hcy can alter human monocyte function by upregulating MCP-1 and IL-8 expression and secretion via enhanced formation of intracellular ROS originated from NAD(P)H oxidase source via calmodulin or protein kinase C signaling pathways and that Hcy-induced ROS subsequently activates mitogen-activated protein kinase (p38 and ERK1/2) and nuclear factor-kappaB in a PPARgamma activator-sensitive manner. Thus, activation of PPARgamma may become a therapeutic target for preventing Hcy-induced proatherogenic effects.
Authors' reply to HESteria or hype?
Authors: O. Faiz, J. Nicholls, A. Darzi
Journal: BMJ (2011)

In reply to Scott and colleagues,1 we found an unequivocally wide variation in reoperation after colorectal surgery. Furthermore, variation is identifiable at high surgical caseloads, suggesting that centralisation of surgical services, a policy commonly applied to reduce variation, may be ineffective. Our duty as researchers is to report variation when it clearly exceeds what would be expected by chance. The extent to …