tbuckley/cabot-search huggingface dataset:
Drug-Induced Blood Dyscrasias
Authors: Allan J. Erslev
Journal: JAMA (1964)

AASTIC ANEMIA is a frequent manifestation L of drug toxicity, and is characterized by pancytopenia and a fatty hypoplastic bone marrow.<sup>1-3</sup>It seems best to restrict the term aplastic anemia to conditions in which the red marrow has been largely replaced by fatty tissue, although normal or even hypercellular foci occasionally may be present. A drug or chemical is believed to play an etiological role in about one half the cases reported. Chloramphenicol appears to be by far the most important offender,<sup>4</sup>but published case reports and those sent to the Registry on Blood Dyscrasias of the American Medical Association attest to the potential bone marrow toxicity of mephenytoin (Mesantoin), sulfonamides, phenylbutazone (Butazolidin), some insecticides and solvents, and many other compounds (Table). However, it is difficult to separate drug-induced from idiopathic cases, and unfortunately there is no test which provides proof of an etiological relationship. Therefore, conclusions must
MAST CELL DEGRANULATION AND HISTAMINE RELEASE OBSERVED IN A NEW IN VITRO SYSTEM
Authors: David Lagunoff, Earl P. Benditt
Journal: The Journal of Experimental Medicine (1960)

A method is described by which mast cells harvested from the rat peritoneal cavity can be deposited on the surface of a Millipore filter without gross injury, permitting observation of morphological and chemical changes induced by a variety of agents. These isolated peritoneal mast cells respond to 48/80 and to polymyxin B but not to dextran or ovomucoid with degranulation and histamine release. Thus four agents which in vivo appear to have similar activities have been found by means of in vitro analysis to operate by at least two different mechanisms.
Mortality risk associated with rheumatoid arthritis in a prospective cohort of older women: results from the Iowa Women's Health Study
Authors: T R Mikuls
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objective:</b> To determine whether rheumatoid arthritis (RA) is associated with excess mortality among older women. <b>Methods:</b> RA associated mortality was examined in a prospective cohort study that was started in 1986, and included 31 336 women aged 55–69 years without a history of RA at baseline. Up to 1997, 158 cases of RA were identified and validated against medical records. The relative risk (RR) and 95% confidence interval (CI) were calculated as measures of association between RA onset and subsequent mortality (overall and cause-specific) using Cox proportional hazards regression. <b>Results:</b> Compared with non-cases, women developing RA during follow up had a significantly increased mortality risk (RR=1.52; 95% CI 1.05 to 2.20). Mortality was higher among rheumatoid factor (RF) positive cases (RR=1.90; 95% CI 1.24 to 2.92) than among RF negative cases (RR=1.00; 95% CI 0.45 to 1.99). There were trends towards increased proportions of RA related deaths from infection (RR=3.61; 95% CI 0.89–14.69) and circulatory disease (RR=1.46; 95% CI 0.76 to 2.81) but not malignancy (RR=0.97; 95% CI 0.46 to 2.04). <b>Conclusions:</b> RA was associated with significantly increased mortality in a cohort of older women, and the association appeared to be restricted to those with RF positive disease.
Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion
Authors: J. M. Thurman
Journal: Journal of Clinical Investigation (2006)

Ischemia/reperfusion (I/R) of several organs results in complement activation, but the kidney is unique in that activation after I/R occurs only via the alternative pathway. We hypothesized that selective activation of this pathway after renal I/R could occur either because of a loss of complement inhibition or from increased local synthesis of complement factors. We examined the relationship between renal complement activation after I/R and the levels and localization of intrinsic membrane complement inhibitors. We found that loss of polarity of complement receptor 1–related protein y (Crry) in the tubular epithelium preceded activation of the alternative pathway along the basolateral aspect of the tubular cells. Heterozygous gene-targeted mice that expressed lower amounts of Crry were more sensitive to ischemic injury. Furthermore, inhibition of Crry expressed by proximal tubular epithelial cells in vitro resulted in alternative pathway–mediated injury to the cells. Thus, altered expression of a complement inhibitor within the tubular epithelium appears to be a critical factor permitting activation of the alternative pathway of complement after I/R. Increased C3 mRNA and decreased factor H mRNA were also detected in the outer medulla after I/R, suggesting that altered synthesis of these factors might further contribute to complement activation in this location.
The Most Solitary of Afflictions: Madness and Society in Britain 1700-1900
Authors: Carl C. Bell
Journal: JAMA (1993)

This text seeks to document the historical reasons for the shift from the medieval British societal response of not segregating the mentally ill to the 19th-century practice of patients being "incarcerated in a specialized, bureaucratically organized, state-supported asylum system which isolated them both physically and symbolically from the larger society." The author notes that medieval England had an unsystematic approach to the care of the mentally ill, and the state had to take more control. In the 18th century these individuals were isolated from society in workhouses, prisons, and hospitals. Since the mentally ill did not fit into these settings, the desire to separate them out began to be a priority, and they became identified as a market. In 1815 a parliamentary inquiry began, and the bad conditions in asylums were exposed. The first attempt at passing reform bills failed owing to their threat to the "mad" business. Since local
The Role of Pulmonary Compliance in the Predominance of Right Pleural Effusion in Congestive Heart Failure.
Authors: E. Lepeschkin
Journal: Annals of Internal Medicine (1961)

s1 May 1961The Role of Pulmonary Compliance in the Predominance of Right Pleural Effusion in Congestive Heart Failure.E. Lepeschkin, M.D.E. Lepeschkin, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1036_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is a common finding that in congestive heart failure pleural effusion is more extensive on the right than on the left side, if no local factors such as pleural adhesions are present to upset this relationship. Many explanations have been advanced to account for this behavior, but none of them are quite satisfactory. The explanation developed by the author is that because the heart is on the left side, the volume of the left lung is smaller than that of the right lung. This difference is even more pronounced in the presence of cardiac hypertrophy or dilatation, which usually... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1961Volume 54, Issue 5Page: 1036-1036KeywordsBehaviorCardiac hypertrophyHeartHeart failureLungsPleural effusion ePublished: 1 December 2008 Issue Published: 1 May 1961 PDF downloadLoading ...
Report of a Case of Complete Heart-block with Autopsy Findings
Authors: WALTER J. WILSON
Journal: Annals of Internal Medicine (1929)

Article1 January 1929Report of a Case of Complete Heart-block with Autopsy FindingsSyphilitic Myocarditis and AortitisWALTER J. WILSONWALTER J. WILSONSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-2-7-669 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptF.A.B., physician, aged 44; married; parent of two apparently healthy children, ten and five years of age respectively.Parental History: Father living and well at 70 years; mother died at 68 years of carcinoma of the rectum and an associated auricular fibrillation and cerebral thrombosis. There is a history of two brothers living and well.Personal History: Army service: At one time had a sore tongue; had a peculiar sensation in the heart after an eighteen-mile walk and had a systolic blood-pressure of 180 while in the service. Military discharge papers call attention to a peculiar heart-sound.Past History: There... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Detroit, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByACUTE GUMMATOUS MYOCARDITIS SIMULATING ACUTE MYOCARDIAL INFARCTION*EDWARD C. REIFENSTEIN, M.D., F.A.C.P. 1 January 1929Volume 2, Issue 7Page: 669-672KeywordsArmed forcesAtrial fibrillationAutopsyChild healthChildrenHeartRectumThrombosisTongue Issue Published: 1 January 1929 PDF DownloadLoading ...
Getting grant applications funded: lessons from the past and advice for the future
Authors: G J Laurent
Journal: Thorax (2004)

Netrin-1 is a neuronal guidance cue that regulates cellular activation, migration, and cytoskeleton rearrangement in multiple cell types. It is a chemotropic protein that is expressed within tissues and elicits both attractive and repulsive migratory responses. Netrin-1 has recently been found to modulate the immune response via the inhibition of neutrophil and macrophage migration. However, the ability of Netrin-1 to interact with lymphocytes and its in-depth effects on leukocyte migration are poorly understood. In this study, we profiled the mRNA and protein expression of known Netrin-1 receptors on human CD4<sup>+</sup> T cells. Neogenin, uncoordinated-5 (UNC5)A, and UNC5B were expressed at low levels in unstimulated cells, but they increased following mitogen-dependent activation. By immunofluorescence, we observed a cytoplasmic staining pattern of neogenin and UNC5A/B that also increased following activation. Using a novel microfluidic assay, we found that Netrin-1 stimulated bidirectional migration and enhanced the size of migratory subpopulations of mitogen-activated CD4<sup>+</sup> T cells, but it had no demonstrable effects on the migration of purified CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>dim</sup> T regulatory cells. Furthermore, using a short hairpin RNA knockdown approach, we observed that the promigratory effects of Netrin-1 on T effectors is dependent on its interactions with neogenin. In the humanized SCID mouse, local injection of Netrin-1 into skin enhanced inflammation and the number of neogenin-expressing CD3<sup>+</sup> T cell infiltrates. Neogenin was also observed on CD3<sup>+</sup> T cell infiltrates within human cardiac allograft biopsies with evidence of rejection. Collectively, our findings demonstrate that Netrin-1/neogenin interactions augment CD4<sup>+</sup> T cell chemokinesis and promote cellular infiltration in association with acute inflammation in vivo.
A SUPPORT FOR PATIENTS SUFFERING WITH WEAKNESS AND PAIN AFTER THE ARREST OF TUBERCULOSIS OF THE SPINE.
Authors: JOHN JOSEPH NUTT
Journal: JAMA (1904)

The relief from weakness and pain, which sometimes remain persistently after all the acute symptoms of tuberculosis of the spine have disappeared, may severely tax the ingenuity and skill of the orthopedist. Because of this fact, this apparatus is presented with the hope that it may be of value to the profession. No originality is claimed, except for the ensemble of its parts, which are taken from well-known braces and applied to a leather corset. This combination, however, proved so serviceable in this instance that others may profit by copying it, in whole or in part. <h3>Patient.</h3> —S. F., aged 27, of Caracas, Venezuela, had developed Pott's disease during early childhood. Until his tenth year he was so weak and sickly that he was not expected to live. He then began to improve, and for the following eight or ten years enjoyed comparatively good health. <h3>History.</h3> —During the past ten
Abstract 1728: Membrane androgen receptor ligands: a novel therapeutic approach for the treatment of cancer
Authors: Konstantinos Alevizopoulos, Nicholas G. Bacopoulos, Christos Stournaras
Journal: Cancer Research (2010)

Abstract Membrane Androgen Receptor (mAR) is a novel, yet of unknown identity, membrane receptor frequently over-expressed in aggressive prostate cancer. mAR is not related to the classical intracellular androgen receptor (AR), a well known therapeutic target for prostate cancer treatment. Consequently, mAR induces tumour cell death by apoptosis in both AR-positive and AR-negative cell lines or in the presence of anti-androgens (e.g. flutamide). Early experimental results with membrane-targeted steroids (androgen-albumin conjugates) have proved the validity of mAR as a novel target of cancer therapy, as based on the anti-cancer action observed in prostate xenograft models (reviewed in IUBMB Life. 2009 Jan;61(1):56-61). In this study, we describe novel small molecule steroidal mAR ligands that exhibit in vitro anti-cancer activity in the nanomolar range in prostate cancer cell lines. Furthermore, and as based on the identification of functional membrane androgen receptors in non-prostate cancer cells by immuno-fluorescence analysis, we show that selective novel mAR ligands exert broad anti-cancer action in additional cell line panels including colon, non-small cell lung cancer, central nervous system, breast or multi drug resistant cells. Notably, our compounds are selective for mAR binding since control displacement assays failed to identify significant interactions with recombinant Androgen Receptors. To assess the anti-cancer of our compounds in vivo, we measured the ability of a prototype mAR ligand, MDX-146, to inhibit tumour growth of human PC-3 prostate cancer xenografts. Our results show clear tumour growth inhibition effects of MDX-146 in animals and propose a potential therapeutic role of specific mAR ligands for the treatment of prostate and other cancers. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1728.
Radionuclide Image Patterns of Hepatic Metastasis and Pyogenic Abscess: Difficulties in Differential Diagnosis
Authors: MICHAEL A. BESS, LLOYD G. BARTHOLOMEW, HEINZ W. WAHNER, MARTIN A. ADSON
Journal: Clinical Nuclear Medicine (1978)

A case of hepatic metastasis with a clinical differential diagnosis of amebic and bacterial abscess is presented. Hepatic scanning with 67Ga-citrate did not diagnostically differentiate the lesion. Hepatic arteriography combined with a therapeutic trial of metronidazole proved useful in defining the lesion. An understanding of the pathophysiologic process involved in 67Ga scanning of hepatic lesions suggests a non-invasive method of discriminating among these clinical diagnostic possibilities.
A comparison of rheumatoid arthritis in Australia and China.
Authors: H Moran, S L Chen, K D Muirden, S J Jiang, Y Y Gu, J Hopper, P L Jiang, G Lawler, R B Chen
Journal: Annals of the Rheumatic Diseases (1986)

A comparison was made of two series of consecutive outpatients with a presumptive diagnosis of rheumatoid arthritis (RA) attending referral centres in Melbourne and Shanghai. No significant differences were observed in disease onset, course, presence of antinuclear antibodies (ANA), or seropositivity. In the Australian series there was a higher frequency of nodules, Raynaud's phenomenon, carpal tunnel syndrome, and 'classical' in comparison with 'definite' disease, and a lower frequency of lymphadenopathy and hepatomegaly. Joint tenderness and soft tissue swelling tended to be more marked in the Chinese series, while deformity and limited range of movement were less severe. Drug therapy was similar overall but influenced by drug availability. Peptic ulceration was recorded in 28% of the Australian series but in only 6% of the Chinese; although 25% of the Chinese were receiving antacids and 6% antiulcerants. X-rays of hands and feet showed more severe disease in the Australian series. The older age group and longer duration of the disease in the Australian patients, who had more chronic and less active disease, may have influenced some of these results.
Preventive Medicine by Risk Factor Analysis
Authors: Daniel G. Miller
Journal: JAMA (1972)

The operational procedures of a preventive medicine clinic have been structured so as to provide selective testing for specific diseases according to a patient's individual risk factors. Diseases included in this program met arbitrarily defined criteria regarding incidence and mortality, benefit of early diagnosis, and availability of satisfactory diagnostic procedures. For each of the diseases which met these criteria, a data reference set was prepared which defined early diagnosis and presented risk factors. Advice rules for the selection of appropriate tests, medical surveillance, and counseling were prepared as procedural logic trees for each disease. The medical record was prepared in a one-page format which lends itself to problem identification, trend analysis, and patient counseling.
Oestrogen and progesterone receptors in lentigo maligna
Authors: M.E. SAWAYA, L.D. GARLAND, M.J. ROTHE, L.S. HONIG, S.L. HSIA
Journal: British Journal of Dermatology (1988)

We have measured oestrogen and progesterone binding in specimens of histopathologically confirmed lentigo maligna (LM) lesions excised from five elderly white men, using a dextran-coated charcoal method. Oestrogen binding was observed in four of the five specimens, and progesterone binding in all five. Marginal normal skin showed only non-specific binding for oestrogen and progesterone. The presence of steroid hormone receptors in LM suggests the possibility that hormone responsiveness may be relevant in the transformation of a lentigo maligna into malignant melanoma.
Haplotype Association Mapping of Acute Lung Injury in Mice Implicates Activin A Receptor, Type 1
Authors: George D. Leikauf, Vincent J. Concel, Pengyuan Liu, Kiflai Bein, Annerose Berndt, Koustav Ganguly, An Soo Jang, Kelly A. Brant, Maggie Dietsch, Hannah Pope-Varsalona, Richard A. Dopico, Y. P. Peter Di, Qian Li, Louis J. Vuga, Mario Medvedovic, Naftali Kaminski, Ming You, Daniel R. Prows
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Because acute lung injury is a sporadic disease produced by heterogeneous precipitating factors, previous genetic analyses are mainly limited to candidate gene case-control studies.Objectives: To develop a genome-wide strategy in which single nucleotide polymorphism associations are assessed for functional consequences to survival during acute lung injury in mice.Methods: To identify genes associated with acute lung injury, 40 inbred strains were exposed to acrolein and haplotype association mapping, microarray, and DNA-protein binding were assessed.Measurements and Main Results: The mean survival time varied among mouse strains with polar strains differing approximately 2.5-fold. Associations were identified on chromosomes 1, 2, 4, 11, and 12. Seven genes (Acvr1, Cacnb4, Ccdc148, Galnt13, Rfwd2, Rpap2, and Tgfbr3) had single nucleotide polymorphism (SNP) associations within the gene. Because SNP associations may encompass "blocks" of associated variants, functional assessment was performed in 91 genes within ± 1 Mbp of each SNP association. Using 10% or greater allelic frequency and 10% or greater phenotype explained as threshold criteria, 16 genes were assessed by microarray and reverse real-time polymerase chain reaction. Microarray revealed several enriched pathways including transforming growth factor-β signaling. Transcripts for Acvr1, Arhgap15, Cacybp, Rfwd2, and Tgfbr3 differed between the strains with exposure and contained SNPs that could eliminate putative transcriptional factor recognition sites. Ccdc148, Fancl, and Tnn had sequence differences that could produce an amino acid substitution. Mycn and Mgat4a had a promoter SNP or 3′untranslated region SNPs, respectively. Several genes were related and encoded receptors (ACVR1, TGFBR3), transcription factors (MYCN, possibly CCDC148), and ubiquitin-proteasome (RFWD2, FANCL, CACYBP) proteins that can modulate cell signaling. An Acvr1 SNP eliminated a putative ELK1 binding site and diminished DNA–protein binding.Conclusions: Assessment of genetic associations can be strengthened using a genetic/genomic approach. This approach identified several candidate genes, including Acvr1, associated with increased susceptibility to acute lung injury in mice.
The colon in medicine: nothing to do with the intestinal tract
Authors: H. Cameron, A. Robertson
Journal: BMJ (1997)

Recent work on systematic reviews led us to reflect on the titles of many medical papers and then wonder why there seemed to be more colons about than before. We report our efforts to explore this gut feeling.

We recorded the number of titles containing at least one colon in the first 100 original or short reports in the BMJ, Lancet, and New England Journal of Medicine every five years from 1970 to 1995. This produced a colon index by year and by editor. The colon indices were subjected to several exploratory tests—the {chi}2 test, the F test, and Student's t test.

All three journals started with a low index, and over time the Lancet and BMJ more often included colons in their titles (1). The {chi}2 test on …
Nocardiosis: a neglected chronic lung disease in Africa?
Authors: G G Baily, P Neill, V J Robertson
Journal: Thorax (1988)

Nocardia organisms were cultured from the sputum of 11 patients at the central hospitals in Harare, Zimbabwe, over a 12 month period. Pulmonary nocardiosis was diagnosed in one further patient on the basis of direct microscopy. Among the nine patients available for follow up, pulmonary nocardiosis was considered to be the major clinical problem in six. The patients usually presented with a chronic pulmonary infection with fever and cough without evidence of dissemination of underlying systemic disease. The chest radiograph showed consolidation in any part of the lung, and this was seen to extend slowly over several months. Prolonged diagnostic delay was a frequent problem. Haemoptysis, alcohol abuse, and empirical treatment for tuberculosis commonly featured in the history. Treatment with sulphonamides was generally successful in those patients who complied. Nocardiosis is a treatable lung disease that may be more common in developing countries than is currently recognised.
The Effect of Group Psychosocial Support on Survival in Metastatic Breast Cancer
Authors: Pamela J. Goodwin, Molyn Leszcz, Marguerite Ennis, Jan Koopmans, Leslie Vincent, Helaine Guther, Elaine Drysdale, Marilyn Hundleby, Harvey M. Chochinov, Margaret Navarro, Michael Speca, Julia Masterson, Liz Dohan, Rami Sela, Barbara Warren, Alexander Paterson, Kathleen I. Pritchard, Andrew Arnold, Richard Doll, Susan E. O'Reilly, Gail Quirt, Nicky Hood, Jonathan Hunter
Journal: New England Journal of Medicine (2001)

Supportive–expressive group therapy has been reported to prolong survival among women with metastatic breast cancer. However, in recent studies, various psychosocial interventions have not prolonged survival.