tbuckley/cabot-search huggingface dataset:
Alteration of topoisomerase II action is a possible molecular mechanism of HL-60 cell differentiation.
Authors: F Gieseler, F Boege, M Clark
Journal: Environmental Health Perspectives (1990)

The inhibition of differentiation and persistence of proliferation in cell transformation is probably not only caused by the mutation of single genes. An additional mechanism of transcriptional control, not only of single genes but of gene programs, is possibly the alteration of the topoisomerases. These enzymes regulate the conformation of DNA by twisting and unwinding the double strands. As has been shown previously, only the genes located in relaxed DNA areas are transcribed and, therefore, the topoisomerases can be described as a gene regulation device. We present the hypothesis that topoisomerase II action is not only altered in, but also necessary for, HL-60 granulocytic cell differentiation. Thus, alteration of topoisomerases may well be a molecular mechanism of cellular differentiation.
Is Cisplatin a Human Carcinogen?
Authors: M. H. Greene
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Is Cisplatin a Human Carcinogen? Get access Mark H. Greene Mark H. Greene * *Correspondence to : Mark H. Grenne, M.D., Hematology/Oncology Section, Department of Internal Medicine, Mayo Clinic Scottsdale, 13400 East Shea Blvd., Scottsdale, Az 85259. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 5, 4 March 1992, Pages 306–312, https://doi.org/10.1093/jnci/84.5.306 Published: 04 March 1992 Article history Received: 30 September 1991 Revision received: 10 January 1992 Accepted: 15 January 1992 Published: 04 March 1992
Carcinoma in Situ
Authors: Robert H. Fennell, Benjamin Castleman
Journal: New England Journal of Medicine (1955)

Skin and Other Nonglandular SurfacesSkinSince the skin is the area most accessible to inspection, it is natural that lesions suspected of being precancerous should be carefully watched for long periods. This was the procedure when Bowen65 (1912), in his original description of "precancerous dermatosis," described its evolution into invasive cancer. This evolution, however, was slow and in 1 of his cases had not occurred in nineteen years. In Bowen's disease all gradations of intermixture of apparently benign and malignant cells may be found, but the malignant cells are limited to the epithelial layers. It was shown that the . . .
Characterization of angiotensin-converting enzyme expression during epidermis morphogenesis in humans: a potential marker for epidermal stem cells
Authors: H-W. Liu, B. Cheng, J-F. Li, H-J. Wu, K-Y. Li, T-Z. Sun, X-B. Fu
Journal: British Journal of Dermatology (2008)

Recent evidence has revealed that angiotensin-converting enzyme (ACE) participates in cutaneous wound healing and contributes to the pathophysiological process of some skin diseases. However, little is known about the role of ACE in epidermis morphogenesis during development.To clarify the expression pattern of ACE during embryonic development of human skin.Skin samples were obtained from aborted fetuses at different gestational ages and from healthy individuals. Localization of ACE, together with beta(1)-integrin, keratin 19 (K19) and p63 was examined by immunofluorescence and immunohistochemical staining.In human fetal skin, at 11-13 weeks of gestation, ACE-positive cells were observed in the primitive epidermis. As the fetuses developed, ACE-positive cells appeared in all the epidermal layers. From 21 weeks of gestation, ACE expression was largely restricted to the basal layer of the fetal epidermis. In contrast, ACE-positive cells were found only in the adult skin basal layer which harbours epidermal stem cells. To explore the possible link between ACE and epidermal stem cells, we further examined the expression of beta(1)-integrin, K19 and p63, the putative markers for epidermal stem cells. Consistent with the results of ACE expression, from 21 weeks of gestation, the expression of beta(1)-integrin, K19 and p63 was mainly confined to the basal layer. Immunofluorescent double labelling revealed that ACE-positive cells substantially overlapped with beta(1)-integrin-, K19- and p63-positive cells.Our results suggest that ACE may play a role in human epidermis morphogenesis during fetal life and serve as an unrecognized marker for keratinocyte progenitor cells.
Development of Efficient Viral Vectors Selective for Vascular Smooth Muscle Cells
Authors: Lorraine M Work, Stuart A Nicklin, Nick J.R Brain, Kate L Dishart, Dan J Von Seggern, Michael Hallek, Hildegard Büning, Andrew H Baker
Journal: Molecular Therapy (2003)

The vascular smooth muscle cell (SMC) is integral to the pathogenesis of neointimal formation associated with late vein graft failure, in-stent restenosis, and transplant arteriopathy. Viral vectors transduce SMC with low efficiency and hence, there is a need for improvement. We aimed to enhance the efficiency and selectivity of gene delivery to human SMC. Targeting ligands were identified using phage display on primary human saphenous vein SMC with linear and cyclic libraries. Two linear peptides, EYHHYNK (EYH) and GETRAPL (GET), were incorporated into the HI loop of adenovirus (Ad) fibers and the capsid protein of adeno-associated virus-2 (AAV-2). Exposure of human venous SMC to EYH-modified (but not the GET-modified) Ad vector resulted in a significant increase in transgene expression levels at short, clinically relevant exposure times. Similarly, the EYH-modified AAV vector resulted in enhanced gene transfer to human venous SMC but not endothelial cells in a time- and dose-dependent manner. The EYH-modified AAV vector also enhanced (up to 70-fold) gene delivery to primary human arterial SMC. Hence, incorporation of EYH into Ad and AAV capsids resulted in a significant and selective enhancement in transduction of SMC and has implications for improving local gene delivery to the vasculature.
Fixed dose procedures for tests on animals.
Authors: A D Dayan
Journal: BMJ (1990)

Barbara, personal communication). A report from New York found that six of 221 patients with cancer who had undergone multiple transfusion had antibodies to HTLV-I, but this high rate has not yet been confirmed elsewhere.20The cost-benefit analysis for screening donors must include the low prevalence of HTLV-I in Britain, the relatively high incidence of false positive reactions, and the low risk of disease developing after infection.Despite these problems the American Red Cross has already begun screening blood donations in the United States for antibodies against HTLV-I, probably in view of potential litigation in the future.Investigation of HTLV-I infection in clinical practice needs to be extended in Britain; it should no longer be confined only to patients from endemic areas as sporadic cases have been reported in low risk populations from most European countries.2'Studies on HTLV-I in Britain to date have been valuable but unplanned and uncoordinated.
Expression Profiling-Based Subtyping Identifies Novel Non-small Cell Lung Cancer Subgroups and Implicates Putative Resistance to Pemetrexed Therapy
Authors: Jun Hou, Margaretha Lambers, Bianca den Hamer, Michael A. den Bakker, Henk C. Hoogsteden, Frank Grosveld, Joost Hegmans, Joachim Aerts, Sjaak Philipsen
Journal: Journal of Thoracic Oncology (2011)
Noninvasive Assessment of Nonalcoholic Fatty Liver Disease in Obese or Overweight Patients
Authors: Sven M.A. Francque, An Verrijken, Ilse Mertens, Guy Hubens, Eric Van Marck, Paul Pelckmans, Peter Michielsen, Luc Van Gaal
Journal: Clinical Gastroenterology and Hepatology (2012)
Pneumoconiosis of Coal-miners.--Part I
Authors: C. M. Fletcher
Journal: BMJ (1948)

In South Wales during the past 15 years rather more than 17,000 men have been certified by the Silicosis Medical Boards to be suffering from silicosis or pneumoconiosis and have been suspended from their underground work.More than 10,000 of them have been certified in the past three trears.There were two mines in South Wales which lost one in every three of their underground workers owing to these diseases in the one year 1945.These bare figures need no embellishment to reveal the seriousness of the problem presented to the mining industry or to convey the extent of human suffering occasioned by pneumoconiosis in this region.Elsewhere in Great Britain the problem' is propor- iionately less serious, but even here the certification of nearly 3,000 men in 15 years presents a problem that is serious enough.In 1943 a committee was set up by the Minister of Fuel and Power to consider the rehabilitation and treat- ment of miners in South Wales suffering from silicosis and pneumoconiosis.Among the recommendations of this committee (Ministry of Fuel and Power, 1944) was that more research into the problem was needed.The Medical research Council was approached, and in 1945 it estab- lished in South Wales a Pneumoconiosis Research Unit to carry out investigations into every aspect of the problem of coal-miners' pneumoconiosis.Since then it has been my.concern to organize and carry out research with a growing team of medical and other scientists in this Unit.I propose, first, to consider briefly how the present adisastrous situation has arisen in a century remarkable for the important advances in industrial health which have been achieved in almost -every industry, then to discuss the former investigations of the Medical Research Council into the problem and the developments that have taken place since their publication.Finally, I shall describe some of the recent investigations undertaken by the Pneumoconiosis Research Unit and others in South Wales. HistoryThe early history of coal-miners' pneumoconiosis is rather obscure.The pathology of the disease was described in this country over 100 years ago in Scottish coal-minets by Gregory (1831), Marshall (1834), and Thomson (1836), and the associated clinical descriptions of the breathlessness, *The first of the two Goulstonian Lectures delivered at the Royal College of Physicians of London on Jan. 13 and 15.tThe Photogravure Plate will appear in next week's issue, with Lecture II.which was called miners' asthma, and the black spit of such cases exactly match the clinical picture as we see it to-day.Greenhow's demonstration of the siliceous residues in the
Nominations open for next year's BMJ Group awards
Authors: N. Hawkes
Journal: BMJ (2009)

The BMJ Group Awards are back—bigger, better, and with a stronger international flavour. Nominations are sought for 11 awards, to be presented at a gala evening at the Hilton, Park Lane, London, next spring.

Last year’s awards attracted a remarkably strong entry and were reported worldwide. The lifetime achievement award, voted for by readers of the BMJ , went to Judith Mackay, a leader in the battle against tobacco. Who’ll win the 2010 award? Nominations close on 15 November, and award winners will be announced on 10 March.

“The 2009 awards were a bit of an experiment for us,” admits Fiona Godlee, editor of the BMJ . “But it was soon clear from the high quality of the entries and from the feedback we got from nominees, winners, and sponsors that we should continue to run the awards. They clearly provide an important platform for celebrating the very best in health care internationally.”

The 2010 awards will show a slight shift in emphasis, with greater importance attached to a theme central to the BMJ Group: getting research into practice. This subject forms a category …
Labour, with Perfect Obliteration of the OS Uteri
Authors: R. G. Mayne
Journal: BMJ (1857)

phthisis.Her complexion was pale and waxy, the lips livid, the respiration laborious, and the cough considerable.There was no expectoration; the pulse was rapid and feeble.She was extremely weak; her voice was low-a faint whisper; and the chief complaint was pain under the left mamma.Mlotion was too painful to allow of a full examination of the chest, and it was only ascertainled that the left side was dull on percussion, and that there was no respiratory murmur there.The cough left her soon after admission, but the other symptoms re- 3mained unchanged.The pain in the side was incessant, and was aggravated by her constantly lying upon it.She was un- able to lie either on the right side or on the back.Nothing gave any relief to the wearing pain.At last, an mdematous ridge was perceptible from the left armpit to the abdomen; the breathina became more difficult, the lips more livid, and the circulation more languid.She slowly but steadily sank, and died about six weeks after her admission.POST MORTaIt EXAMINATION, twenty-four hours after deatl, July 24th.Decomposition had set in to such an extent that a very strict examination was all but impossible.It was ascer- tained, however, that the left pleural cavity was fnll of blood, and that it was making its way to the surface.The cartilages of the third, fourth, and fifth ribs, and a small portion of the bones, were partially absorbed.The intercostal muscles had
SUGGESTION ON THE USE OF ELECTRICITY IN EAR DISEASES.Read in the Section of Laryngology and Otology at the Forty first Annual Meeting of the American Medical Association, Nashville, Tenn., May, 1890.
Authors: E. L. JONES
Journal: JAMA (1890)

When I received an invitation from your Secretary to prepare a paper for the Section of Laryngology and Otology, my first thought was to decline, on the ground that it would seem like presumption for me to appear in the rôle of instructor to those so much my seniors in authority and experience as the members of this learned body. The remarks which I shall make at least present the merit of originality, so far as my knowledge goes, and the frequent occurrence and incurable nature of the affections to which they pertain certainly demands our thoughtful consideration of anything that may benefit the vast multitude whose hearing is impaired or lost through these diseases. My conclusions are based largely on the successful applications of these principles to analogous conditions elsewhere, and somewhat on the results of a limited personal experience. Just here I
Cationic protein-induced sensory nerve activation: role of substance P in airway hyperresponsiveness and plasma protein extravasation.
Authors: A J Coyle, F Perretti, S Manzini, C G Irvin
Journal: Journal of Clinical Investigation (1994)

We have previously reported that human eosinophil granule major basic protein and synthetic cationic proteins such as poly-L-arginine and poly-L-lysine, can increase airway responsiveness in vivo. In the present study, we have investigated whether activation of sensory C-fibers is important in this phenomenon. Dose-response curves to methacholine were constructed before and 1 h after intratracheal instillation of poly-L-lysine in anaesthetized spontaneously breathing rats, and the concentration of methacholine required to induce a doubling in total lung resistance was calculated. Poly-L-lysine induced a fivefold increase in airway responsiveness, which was inhibited by neonatal capsaicin treatment and potentiated by phosphoramidon (100 micrograms/ml). Furthermore, pretreatment with either CP, 96-345, or RP-67580 two selective NK-1 receptor antagonists inhibited poly-L-lysine-induced airway hyperresponsiveness and plasma protein extravasation. In vitro, cationic proteins stimulated the release of calcitonin gene-related peptide-like immunoreactivity from perfused slices of the main bronchi. Our results demonstrate that cationic proteins can activate sensory C-fibers in the airways, an effect which is important in the subsequent development of airway hyperresponsiveness and plasma protein extravasation. Cationic proteins may therefore function as a link between inflammatory cell accumulation and sensory nerve activation.
A Randomized Trial Evaluating a Predominately Fetal Growth–Based Strategy to Guide Management of Gestational Diabetes in Caucasian Women
Authors: Ute M. Schaefer-Graf, Siri L. Kjos, Ostary H. Fauzan, Kai J. Bühling, Gerda Siebert, Christoph Bührer, Barbara Ladendorf, Joachim W. Dudenhausen, Klaus Vetter
Journal: Diabetes Care (2004)

OBJECTIVE—To compare the management of Caucasian women with gestational diabetes (GDM) based predominantly on monthly fetal growth ultrasound examinations with an approach based solely on maternal glycemia. RESEARCH DESIGN AND METHODS—Women with GDM who attained fasting capillary glucose (FCG) &amp;lt;120 mg/dl and 2-h postprandial capillary glucose (2h-CG) &amp;lt;200 mg/dl after 1 week of diet were randomized to management based on maternal glycemia alone (standard) or glycemia plus ultrasound. In the standard group, insulin was initiated if FCG was repeatedly &amp;gt;90 mg/dl or 2h-CG was &amp;gt;120 mg/dl. In the ultrasound group, thresholds were 120 and 200 mg/dl, respectively, or a fetal abdominal circumference &amp;gt;75th percentile (AC&amp;gt;p75). Outcome criteria were rates of C-section, small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infants, neonatal hypoglycemia (&amp;lt;40 mg/dl), and neonatal care admission. RESULTS—Maternal characteristics and fetal AC&amp;gt;p75 (36.0 vs. 38.4%) at entry did not differ between the standard (n = 100) and ultrasound groups (n = 99). Assignment to (30.0 vs. 40.4%) and mean duration of insulin treatment (8.3 vs. 8.1 weeks) did not differ between groups. In the ultrasound group, AC&amp;gt;p75 was the sole indication for insulin. The ultrasound-based strategy, as compared with the maternal glycemia-only strategy, resulted in a different treatment assignment in 34% of women. Rates of C-section (19.0 vs. 18.2%), LGA (10.0 vs. 12.1%), SGA (13.0 vs. 12.1%), hypoglycemia (16.0 vs. 17.0%), and admission (15.0 vs. 14.1%) did not differ significantly. CONCLUSIONS—GDM management based on fetal growth combined with high glycemic criteria provides outcomes equivalent to management based on strict glycemic criteria alone. Inclusion of fetal growth might provide the opportunity to reduce glucose testing in low-risk pregnancies.
US faces looming cost of ischaemic stroke
Authors: J. Tanne
Journal: BMJ (2006)

In the next half century, the United States will face an “enormous” burden of stroke, estimated at a total $2.2 trillion. The cost will disproportionately affect its Hispanic and African-American populations, a study published online on 16 August in Neurology has found (doi: 10.1212/01.wnl.0000237024.16438.20).

“Stroke is the third leading cause of death in the United States and the leading cause of adult disability,” the study says. The study looked at the projected costs of ischaemic stroke from 2005 to 2050 in non-Hispanic white, Hispanic, and African-American people. The greatest economic effect will be lost earnings, the authors conclude, followed by the cost of rehabilitation.

Hispanic and African-American US citizens have higher incidences of ischaemic stroke than their …
An Introduction to Vertebrate Embryology. Based on the Study of the Frog and the Chick.
Authors: Albert Moore Reese
Journal: JAMA (1904)

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Rabies Prophylaxis-Reply
Authors: Michael Hattwick
Journal: JAMA (1975)

<h3>In Reply.—</h3> Dr Weis' comments are well taken and correct, and we fully endorse and support them. Whenever it is possible to obtain prompt results of a laboratory examination on a possibly rabid animal, the decision to treat the exposed person can, we think, be reasonably delayed until that result is available. However, if practical difficulties make it impossible to obtain prompt laboratory results, prophylaxis should be started. If the laboratory tests show that the animal was not rabid, treatment can be discontinued. In general, rabies postexposure prophylaxis is most effective when given as soon after exposure as practicable; delay in starting prophylaxis does reduce its efficacy. We thank Dr Weis for emphasizing this important point.
Antitumor Activity of a Humanized, Bivalent Immunotoxin Targeting Fn14-Positive Solid Tumors
Authors: Hong Zhou, Walter N. Hittelman, Hideo Yagita, Lawrence H. Cheung, Stuart S. Martin, Jeffrey A. Winkles, Michael G. Rosenblum
Journal: Cancer Research (2013)

The TNF-like weak inducer of apoptosis (TWEAK; TNFSF12) receptor Fn14 (TNFRSF12A) is expressed at low levels in normal tissues but frequently highly expressed in a wide range of tumor types such as lung, melanoma, and breast, and therefore it is a potentially unique therapeutic target for these diverse tumor types. We have generated a recombinant protein containing a humanized, dimeric single-chain anti-fibroblast growth factor-inducible 14-kDa protein (Fn14) antibody fused to recombinant gelonin toxin as a potential therapeutic agent (designated hSGZ). The hSGZ immunotoxin is a highly potent and selective agent that kills Fn14-positive (Fn14(+)) tumor cells in vitro. Treatment of cells expressing the MDR protein MDR1 (ABCB1B) showed no cross-resistance to hSGZ. Induced overexpression of Fn14 levels in MCF7 cells through HER2 (ERBB2) signaling translated to an improved therapeutic index of hSGZ treatment. In combination with trastuzumab, hSGZ showed an additive or synergistic cytotoxic effect on HER2(+)/Fn14(+) breast cancer cell lines. Also, hSGZ treatment inhibited Erb3/Akt signaling in HER2-overexpressing breast cancer cells. Pharmacokinetic studies in mice revealed that hSGZ exhibited a biexponential clearance from plasma with a rapid initial clearance (t1/2α = 1.26 hours) followed by a seven-fold longer plasma half-life (t1/2β = 7.29 hours). At 24, 48, and 72 hours after injection, uptake of the hSGZ into tumors was 5.1, 4.8, and 4.7%ID/g, with a tumor-to-muscle ratio of 5.6, 6.2, and 9.0, respectively. Therapeutic efficacy studies showed significant tumor inhibition effects using an MDA-MB-231/Luc breast cancer xenograft model. Our findings show that hSGZ is an effective anticancer agent and a potential candidate for clinical studies.
Reversible plane xanthoma, vasculitis, and peliosis hepatis in giant lymph node hyperplasia (Castleman's disease): A case report and review of the cutaneous manifestations of giant lymph node hyperplasia
Authors: D. Sherman, B. Ramsay, N.A. Theodorou, D. Woodrow, F.P. Paradinas, J.J. Cream, I.M. Murray-Lyon
Journal: Journal of the American Academy of Dermatology (1992)