tbuckley/cabot-search huggingface dataset:
Comparative activity of human carcinogens and NTP rodent carcinogens in the mouse bone marrow micronucleus assay: an integrative approach to genetic toxicity data assessment.
Authors: H Tinwell, J Ashby
Journal: Environmental Health Perspectives (1994)

The mouse bone marrow micronucleus (MN) assay holds a key position in all schemes for detecting potential human carcinogens and mutagens. It was therefore of concern when Shelby et al. reported that only 5 of 25 rodent carcinogens defined by the U.S. NTP were positive in the assay. Further, each of these positive responses was weak and indistinguishable from the 4 positive responses observed among the 24 NTP noncarcinogens tested. To focus these findings, the activity in the MN assay of 26 human carcinogens, 6 reference rodent genotoxins, and the 9 NTP chemicals positive in the MN assay have been displayed in a common format. This involved plotting the minimum positive dose level (expressed as mumole/kilogram) and the maximum fold-increase in micronucleated polychromatic erythrocytes frequency observed at any dose level. By displaying the high sensitivity of the micronucleus assay to the reference human and rodent genotoxins, this analysis emphasizes the weakness in the MN assay responses given by the NTP carcinogens reported by Shelby et al. This, in turn, poses questions about the intrinsic hazard of this selection of NTP rodent carcinogens. Using fotemustine and vitamin C as models of a toxic and a nontoxic chemical known to be active in the MN assay, this analysis describes a method by which their relative potential human hazard can be distinguished (a synthetic, as opposed to an analytical approach to data assessment). The possibility that some weak responses observed in the MN assay at elevated dose levels may be stress induced is considered.
Parathyroidectomy in ESRD
Authors: Eric P. Cohen, John E. Moulder
Journal: Kidney International (2004)

To the Editor: Kestenbaum et al have confirmed that parathyroidectomy rates in the United States have fallen since 1990, and, in an accompanying editorial, a plea is made for improved management of secondary hyperparathyroidism1.Kestenbaum B. Seliger S.L. Gillen D.L. et al.Parathyroidectomy rates among United States dialysis patients: 1990–1999.Kidney Int. 2004; 65: 282-288Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar,2.Goodman W.G. Medical control of secondary hyperparathyroidism: We're not there yet.Kidney Int. 2004; 65: 335-336Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar. We agree completely that use of parathyroidectomy has declined in the United States, and we reported this in 20013.Cohen E.P. Moulder J.E. Parathyroidectomy in chronic renal failure: Has medical care reduced the need for surgery?.Nephron. 2001; 89: 271-273Crossref PubMed Scopus (33) Google Scholar. Similar findings were reported from Japan4.Tokuyama K. Iseki K. Yoshi S. et al.An epidemiologic analysis of parathyroidectomy in chronic dialysis patients. The Okinawa dialysis study group.Jpn J Nephrol. 1996; 38: 309-313Google Scholar. But use of parathyroidectomy rates is an imperfect yardstick of the management of secondary hyperparathyroidism. Use of parathyroidectomy is a low-frequency occurrence, affecting less than one dialysis patient per 100 per year. It is possible that there is a small but ineradicable fraction of end-stage renal disease (ESRD) patients who will respond poorly to medical management of secondary hyperparathyroidism, and will thus ultimately require what amounts to parathyroid debulking. Just because parathyroidectomies are still needed in 2003 does not mean that we are doing a bad job with our current management of secondary hyperparathyroidism. Recent data suggest that the time from first ESRD to parathyroidectomy has lengthened significantly over the past decade, and is now a median of six years [abstract; Cohen EP, J Am Soc Nephrol 14:684a, 2003]. It is possible that indications for parathyroidectomy have gradually and linearly changed over this time. But that seems unlikely. Thus, current medical management—better dialysis, better phosphate binders, use of vitamin D analogs—appears to have had an impact. Use of this surgery, and time-to-need-for-surgery, has evolved in a favorable direction. New agents, such as calcimimetics, may improve more subtle aspects of secondary hyperparathyroidism, but may not materially affect parathyroidectomy rates.
Is the gap between guidelines and clinical practice in heart failure treatment being filled? Insights from the IMPACT RECO survey
Authors: P. de Groote, R. Isnard, P. Assyag, P. Clerson, A. Ducardonnet, M. Galinier, G. Jondeau, I. Leurs, J.‐F. Thébaut, M. Komajda
Journal: European Journal of Heart Failure (2007)
THREE-MONTH CUMULATIVE INCIDENCE OF THROMBOEMBOLISM AND BLEEDING AFTER PERIPROCEDURAL ANTICOAGULATION MANAGEMENT OF PATIENTS WITH VENOUS THROMBOEMBOLISM
Authors: Robert D. McBane, Waldemar E. Wysokinski, Paul R. Daniels, Scott Litin, Joshua Slusser, David Hodge, John A. Heit
Journal: Journal of the American College of Cardiology (2010)
Varicella Vaccine: Decisions a Little Nearer
Authors: Kenneth McIntosh
Journal: New England Journal of Medicine (1984)

The live attenuated varicella vaccines have generated much discussion. In the late 1970s, while the Japanese were testing their vaccine strains and publishing their results in American journals, the journal-reading pediatric community was treated to a veritable torrent of editorial and epistolary opinion on the merits and demerits of proceeding with clinical trials on home territory.1 2 3 4 There were many bothersome questions that surfaced in those printed pages. Was the vaccine needed in the first place? After all, zoster immune globulin could be used to prevent varicella in the highest risk group, and chickenpox in normal children was considered fairly benign. . . .
Alcohol Injections in Hodgkin's Disease, Etc.
Authors: A. F. Bock
Journal: JAMA (1898)

St. Louis, Mo., July 13, 1898. <h3>To the Editor:</h3> —The undersigned is preparing a paper on his experience with injection of alcohol in cases of Hodgkin's disease and cancer of the stomach and for the present will only say that the results thus far have been very encouraging. In due time he will send you a full report for publication. Respectfully,
Hepatitis G Virus — A True Hepatitis Virus or an Accidental Tourist?
Authors: Yuzo Miyakawa, Makoto Mayumi
Journal: New England Journal of Medicine (1997)

Over the past 30 years, five hepatitis viruses have been identified and named A, B, C, D, and E.1 Hepatitis A and E viruses are transmitted enterically and induce acute hepatitis, but they rarely cause chronic hepatitis. Hepatitis B virus (HBV) and hepatitis C virus (HCV), by contrast, are primarily blood-borne, cause acute as well as chronic hepatitis, and can lead to cirrhosis and hepatocellular carcinoma. Hepatitis D, or delta virus, is exceptional in that it is dependent on HBV and can modify the disease associated with that virus.Acute or chronic hepatitis in which both nonviral causes and infection . . .
Raised serum levels of cachectin/tumor necrosis factor alpha in renal allograft rejection.
Authors: C P Maury, A M Teppo
Journal: The Journal of Experimental Medicine (1987)

A sensitive radioimmunoassay was used for monitoring serum levels of endogenous cachectin/tumor necrosis factor alpha (TNF) in 10 renal transplant recipients. Acute allograft rejections were associated with marked elevations of circulating TNF. The peak levels of TNF (median 140 pg/ml) were in the same concentration range as previously reported in parasitic infections. The results show that the release of TNF into circulation is an early event in renal allograft rejection and that raised levels of TNF in man can also be induced by noninfectious stimuli.
Effect of Once-Daily (qd) Budesonide/Formoterol Pressurized Metered-Dose Inhaler (BUD/FM pMDI) on Forced Expiratory Flow Between 25% and 75% (FEF25-75%) in Children and Adolescents (Aged 6-11 and 12-15 Years) With Asthma Previously Stable on Twice-Daily (bid) BUD/FM pMDI
Authors: S.M. Meltzer, T. Uryniak, C.D. O'Brien, K. Lampl
Journal: Journal of Allergy and Clinical Immunology (2009)
90. In Vitro and In Vivo Gene Expression of Lentiviral Vectors in CD4+ T Cells
Authors: Kit L. Shaw, Karen Pepper, Denise Petersen, Vesa Kaartinen, Donald B. Kohn
Journal: Molecular Therapy (2005)

In certain applications of gene therapy, regulated (rather than constitutive) gene expression will be crucial for proper function or optimal effect of the delivered gene. Therefore, an important goal of gene therapy is to be able to deliver genes so that they express in a pattern that recapitulates the expression of an endogenous cellular gene. Additionally, regulating transgene expression will be an important component of efforts for reducing risks of adverse advents associated with gene therapy with integrating vectors.
Comparison of dermoscopic and histopathological findings in a mucous melanoma of the lip
Authors: S. Matsushita, T. Kageshita, T. Ishihara
Journal: British Journal of Dermatology (2005)

Journal Article Comparison of dermoscopic and histopathological findings in a mucous melanoma of the lip Get access S. Matsushita, S. Matsushita Departments of Plastic and Reconstructive Surgery and Dermatology, Graduate School of Medical Sciences, Kumamoto University, 1‐1‐1 Honjo, Kumamoto 860‐8556, Japan S. Matsushita. E‐mail: shigeto0302@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar T. Kageshita, T. Kageshita Departments of Plastic and Reconstructive Surgery and Dermatology, Graduate School of Medical Sciences, Kumamoto University, 1‐1‐1 Honjo, Kumamoto 860‐8556, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Ishihara T. Ishihara Departments of Plastic and Reconstructive Surgery and Dermatology, Graduate School of Medical Sciences, Kumamoto University, 1‐1‐1 Honjo, Kumamoto 860‐8556, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 6, 1 June 2005, Pages 1324–1326, https://doi.org/10.1111/j.1365-2133.2005.06463.x Published: 01 June 2005 Article history Accepted: 25 September 2004 Published: 01 June 2005
Complement in overt and asymptomatic nephritis after skin infection
Authors: C. Warren Derrick, Mary Sue Reeves, Hugh C. Dillon
Journal: Journal of Clinical Investigation (1970)

In an ongoing study of streptococcal skin infection and acute glomerulonephritis (AGN) begun in 1964, C′3 determinations were done in 784 patients. There were 126 patients with acute poststreptococcal nephritis, 172 of their siblings, and 486 patients with uncomplicated impetigo from families without an index case of nephritis.
Commercialisation of health care in US distorts resource allocation, expert says
Authors: David Spurgeon
Journal: BMJ (2008)

The failure of the United States to contain medical costs, which now exceed $2.1 trillion (£1.1 trillion; €1.4 trillion) a year or more than $7000 for every man, woman, and child in the country, results primarily from the unique and pervasive commercialisation of the sector, an article in this week’s New England Journal of Medicine says (2008;358:549-51).

Inthe perspective article Robert Kuttner, coeditor of the magazine The American Prospect and a senior fellow at Demos, a public policy research and advocacy organisation based in New York, contends that what raises costs and distorts resource allocation are “the dominance of for-profit insurance and pharmaceutical companies, a new wave of investor-owned specialty …
THE RADICAL ABDOMINAL OPERATION FOR CARCINOMA OF THE CERVIX UTERI: Result of One Hundred Cases Reckoned on an Absolute Cure Basis
Authors: C. Berkeley, V. Bonney
Journal: BMJ (1916)

upon 100 cases of carcinioma of the cervix uteri by the radical abdominal nmetlhod.Thie timne hias tlherefore come when we can review our results from tlle point of view of absolute cure, or five years' freedom from recurrence, for it is agreed that patients wlho have survived this period without return of the growth may be regarded as cured.
Abstract 4462: Resistance to selective kinase inhibitors upon epithelial to mesenchymal transition.
Authors: Catherine R. Wilson, Katrina Nicholes, Daisy Bustos, Eva Lin, Lily Shi, Donald Kirkpatrick, Jeffrey Settleman
Journal: Cancer Research (2013)

Abstract Epithelial to mesenchymal transition (EMT) is a pivotal mechanism contributing to cancer metastasis and has been associated with resistance to multiple cancer therapies including targeted kinase inhibitors (TKIs). EMT has been associated with an acquired resistance to the EGFR TKI erlotinib independent of known resistance mechanisms such as secondary mutations T790M or MET amplification. RTK-addicted cancer cell lines that are induced to undergo EMT with exogenous TGF-β become resistant to their appropriate TKI. In vitro-based assays determined that the resistance is not due to exogenous TGF-β, drug efflux, or autocrine/paracrine growth factor signaling. To identify potential therapeutic vulnerabilities specifically within the mesenchymal, TKI resistant cells, we performed a small molecule screen of approximately 200 agents using the EGFR mutant non-small cell lung cancer (NSCLC) HCC827 cell line and its corresponding TGF-β-induced mesenchymal derivative line. This screen revealed that the mesenchymal cells are cross-resistant to a variety of small molecules, including TKIs and chemotherapeutic agents. However, a small number of agents showed selective growth inhibitory activity against the mesenchymal cells, with the most potent being the dual Brc-Abl and Src inhibitor, dasatinib. Within the parental HCC827 cell line, we detected a non-proliferating vimentin positive sub-population of cells. Interestingly, when the parental cell line was co-treated with erlotinib and dasatinib the entire cell population was killed and drug-resistant clones failed to emerge after prolonged treatment. To determine the mechanism underlying the resistance observed within the mesenchymal cells a proteomic analysis was undertaken, which demonstrated that the focal adhesion kinase, FAK, is the most abundant differentially phosphorylated protein in the resistant mesenchymal cells that is specifically suppressed by dasatinib. However, specific gene knock-down of FAK was not sufficient to kill the mesenchymal cells or revert their sensitivity to Erlotinib suggesting that FAK alone is not required to maintain resistance upon EMT. These findings identify dasatinib as a potential therapeutic for treatment of erlotinib resistance associated with EMT. Citation Format: Catherine R. Wilson, Katrina Nicholes, Daisy Bustos, Eva Lin, Lily Shi, Donald Kirkpatrick, Jeffrey Settleman. Resistance to selective kinase inhibitors upon epithelial to mesenchymal transition. [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 4462. doi:10.1158/1538-7445.AM2013-4462
Acute 99mTc DMSA Scan Predicts Dilating Vesicoureteral Reflux in Young Children With a First Febrile Urinary Tract Infection
Authors: Ji-Nan Sheu, Kang-Hsi Wu, Shan-Ming Chen, Jeng-Dau Tsai, Yu-Hua Chao, Ko-Huang Lue
Journal: Clinical Nuclear Medicine (2013)

This study aimed to examine the ability of acute (99m)Tc DMSA scan for predicting dilating (grades III-V) vesicoureteral reflux (VUR) after a first febrile urinary tract infection in children aged 2 years or younger.All children underwent ultrasonography (US), (99m)Tc DMSA scan, and voiding cystourethrography. Sensitivity, specificity, positive and negative predictive values, likelihood ratios, and receiver operating characteristic curves were performed to assess the diagnostic accuracy for predicting dilating VUR. Follow-up scan was performed at least 6 months after the acute infection to evaluate the presence of renal scarring (RS) or new scars.Of the 473 children analyzed (289 boys and 184 girls; median age, 5 months), 282 (59.6%) had abnormal acute (99m)Tc DMSA scan findings. There was VUR in 153 children (32.3%), whereas 95 (20.1%) had dilating VUR. The sensitivity and negative predictive value in predicting dilating VUR were 95.8% and 97.9%, respectively, for (99m)Tc DMSA and 97.9% and 98.6%, respectively, for combined US and (99m)Tc DMSA, whereas the positive and negative likelihood ratios were 1.90 and 0.08, respectively, for (99m)Tc DMSA and 1.57 and 0.06, respectively, for combined studies. On multivariate analysis, dilating VUR was a predictor for developing RS and new scars.Our results reveal the usefulness of acute (99m)Tc DMSA scan for predicting dilating VUR in children with a first febrile urinary tract infection. A voiding cystourethrography is indicated in only children with abnormalities found on a (99m)Tc DMSA and/or a US. The presence of dilating VUR predisposes to developing RS and new scars.
Gene silencing as a threat to the success of gene therapy
Authors: Timothy H. Bestor
Journal: Journal of Clinical Investigation (2000)

Eukaryotes deploy elaborate defensive systems to protect the structure of their genomes and to oppose the expression of abnormal or alien transcription units. In mammals, the insertion of retroviral DNA or the incorporation of repeat arrays can trigger transcriptional silencing of the inserted sequences, usually via mechanisms that involve methylation of DNA within regulatory regions. Fungi and plants have similar methylation-based systems and also employ diverse post-transcriptional mechanisms to reduce or eliminate the expression of alien transcription units, mechanisms that operate even in organisms that apparently lack the capacity to methylate their DNA. Given their ubiquity in other eukaryotes, it is likely that similar post-transcriptional silencing mechanisms will be found to operate in mammals as well. I argue here that gene silencing mechanisms are diverse and efficient and are likely to represent a barrier to many forms of gene therapy. For this reason, it will be necessary to develop gene therapy vectors that are both resistant to host defensive measures and efficient in terms of delivery and expression.
Depressive Disease: Familial Psychiatric Illness
Authors: JOE DORZAB, MAX BAKER, REMI J. CADORET, GEORGE WINOKUR
Journal: American Journal of Psychiatry (1971)

Data from families of 100 intensively studied patients with depressive disease (unipolar affective disorder) and a review of the literature suggest that genetic factors play a role in the etiology of depressive disease. It is also possible that this disease may in fact be a heterogeneous group of illnesses with different manifestations, for example, in males and females. The authors stress the need for further studies to test their hypothesis.
Liverpool care pathway is a half baked compromise
Authors: C. Brewer
Journal: BMJ (2012)

Although the Liverpool care pathway (LCP) seems to be the palliative care version of very slow active euthanasia by very slow lethal injection,1 in practice it is a half baked compromise. An old friend of mine recently died on a LCP regimen. She was already sedated with midazolam to the point of unresponsiveness when I was called to visit her and was told that she …
213. PEG-Modified Cationic Gold Nanoparticles and Their Abilities of In Vivo Gene Delivery
Authors: Takahito Kawano, Yasuro Niidome, Yoshiki Katayama, Takuro Niidome
Journal: Molecular Therapy (2005)

Previously, we reported that cationic gold nanoparticles, prepared by reducing HAuCl4 with NaBH4 in the presence of the 2-aminoethanethiol (AET), formed complexes with plasmid DNA. The complexes showed transfection ability (Niidome et al., Chem. Commun. 2004, 1978-1979 (2004)). Since characteristics of the inorganic nanoparticles differ from that of organic molecules, they are expected to be a novel base-material for gene delivery. However, the gold nanoparticles can't be stored for one month and more in aqueous solution because of formation of aggregation between the particles. In addition, the DNA complex also slowly grew up to more than 2,000 nm. In this study, to obtain highly stable and colloidal nanoparticle, we modified the cationic gold nanoparticles with PEG chains. The modification by the PEG is also expected to provide stealth character in vivo, which enable us targeted gene delivery.
Multipotent hematopoietic cell lines derived from C/EBPα(−/−) knockout mice display granulocyte macrophage–colony-stimulating factor, granulocyte– colony-stimulating factor, and retinoic acid–induced granulocytic differentiation
Authors: Steven J. Collins, Jon Ulmer, Louise E. Purton, Gretchen Darlington
Journal: Blood (2001)
Hyper-Endorphin Syndrome in a Child with Necrotizing Encephalomyelopathy
Authors: Niels Jacob Brandt, Lars Terenius, Bendt Brock Jacobsen, Leif Klinken, Åsa Nordius, Sven Brandt, Karin Blegvad, Minna Yssing
Journal: New England Journal of Medicine (1980)

SUBACUTE necrotizing encephalomyelopathy, or Leigh's syndrome, 1 is a degenerative disorder characterized by progressive deterioration of brain-stem functions, ataxia, convulsions, hypotonia, and failure to thrive. The histopathologic changes are found in the brain stem, basal ganglia, cerebellar cortex, and dentate nucleus, and they consist of bilateral symmetrical areas of rarefaction, loss of myelin, and cell proliferation in the capillaries and glia. This disorder occurs in infancy and early childhood and is inherited as an autosomal-recessive trait, but the basic biochemical defect is unknown.We report on a syndrome in a boy suffering from attacks mimicking acute morphine poisoning with prolonged apnea . . .
Competition, Regulation, and Hospital Cost-Reply
Authors: Harold S. Luft
Journal: JAMA (1989)

<h3>In Reply. —</h3> Mr Mendelson's comparison of our figures with those from 1978 through 1982 is misleading, since we focus on rates of hospital cost inflation after adjusting for changes in wage rates, involvement in medical education, and other factors, while he focuses on unadjusted cost-inflation figures. We have no adjusted inflation figures for 1978 through 1982, but, as part of recent work, we have calculated adjusted rates of inflation for the entire decade from 1972 through 1982, which can be compared with adjusted inflation figures for 1982 through 1986. While Mr Mendelson's unadjusted figures show large differences between Massachusetts and the rest of the nation for 1978 through 1982, our figures show Massachusetts hospitals to have an adjusted rate of inflation from 1972 through 1982 only 1.8% lower than that of the rest of the nation (excluding Maryland, New York, New Jersey, and California), a statistically insignificant figure (<i>P</i>
Safety and Side Effects of Sustained-Release Niacin-Reply
Authors: James M. McKenney
Journal: JAMA (1994)

In Reply.  —Niacin remains a valuable agent for the treatment of dyslipidemias and is properly categorized as a major drug for managing hypercholesterolemia in the new Adult Treatment Panel (ATPII) guidelines. 1 As a grandfathered drug, it has not been subjected to the rigorous, systematic study the Food and Drug Administration requires for approval and marketing of modern drugs, and we must continue to learn about it unless and until it becomes displaced by newer and safer drugs.  Dr Keenan and colleagues are critical of the 1500 mg twice-daily dosing schedule we used. This dose is not excessive by current standards. 2 We do not find any reports supporting the notion that thrice-daily dosing of niacin is safer, more effective, or more physiologic. Optimal dosing of niacin may not be achieved until we have a better understanding of its pharmacokinetics. Contrary to his suggestion that it was intentional, the frequency