tbuckley/cabot-search huggingface dataset:
Splenectomy in the Treatment of Rheumatoid arthritis : A Report of Three Cases
Authors: F. Bach, O. Savage
Journal: Annals of the Rheumatic Diseases (1940)

Still read a paper on " A Form of Chronic Joint Disease in Children."He described a form of chronic polyarthritis of childhood beginning before the second dentition, and characterised by chronic progressive enlargement of joints with- out bony change and by general enlargement of the glands and of the spleen.In 1924 Dr. A. R. Felty published a paper in the Johns Hopkins Hospital Bulletin entitled " Chronic Arthritis in the Adult associated with Splenomegaly and Leukopenia."He described five middle-aged patients, three men and two women, suffering from chronic arthritis, with enlargement of the spleen, leukopenia and enlarged lymphatic glands.In every case a yellowish-brown pigmentation of the skin was noticed.All were undernourished and gave a history of marked loss of weight since the onset of symptoms.In every instance the arthritis was long-standing, and the spleen was palpably enlarged, firm but not tender.There was a slight anaemia and a leukopenia, the white cells varying between 1,000 and 4,000 per cubic millimetre.Two of the patients ran a low fever for some weeks.Dr. Felty appears to have been uncertain whether to classify these cases as an adult form of the syndrome described by Still, or as two separate entities-Banti's disease and chronic arthritis-occurring concurrently in the same individual.He presented them as examples of a distinct clinical entity of unknown origin.
The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers
Authors: Eugene V Koonin, Kira S Makarova, Igor B Rogozin, Laetitia Davidovic, Marie-Claude Letellier, Luca Pellegrini
Journal: Genome biology (2003)

The rhomboid family of polytopic membrane proteins shows a level of evolutionary conservation unique among membrane proteins. They are present in nearly all the sequenced genomes of archaea, bacteria and eukaryotes, with the exception of several species with small genomes. On the basis of experimental studies with the developmental regulator rhomboid from Drosophila and the AarA protein from the bacterium Providencia stuartii, the rhomboids are thought to be intramembrane serine proteases whose signaling function is conserved in eukaryotes and prokaryotes.Phylogenetic tree analysis carried out using several independent methods for tree constructions and the corresponding statistical tests suggests that, despite its broad distribution in all three superkingdoms, the rhomboid family was not present in the last universal common ancestor of extant life forms. Instead, we propose that rhomboids evolved in bacteria and have been acquired by archaea and eukaryotes through several independent horizontal gene transfers. In eukaryotes, two distinct, ancient acquisitions apparently gave rise to the two major subfamilies, typified by rhomboid and PARL (presenilins-associated rhomboid-like protein), respectively. Subsequent evolution of the rhomboid family in eukaryotes proceeded by multiple duplications and functional diversification through the addition of extra transmembrane helices and other domains in different orientations relative to the conserved core that harbors the protease activity.Although the near-universal presence of the rhomboid family in bacteria, archaea and eukaryotes appears to suggest that this protein is part of the heritage of the last universal common ancestor, phylogenetic tree analysis indicates a likely bacterial origin with subsequent dissemination by horizontal gene transfer. This emphasizes the importance of explicit phylogenetic analysis for the reconstruction of ancestral life forms. A hypothetical scenario for the origin of intracellular membrane proteases from membrane transporters is proposed.
Intravascular Hemolysis As a Complication of Clostridium Perfringens Sepsis
Authors: Heather L. McArthur, Bakul I. Dalal, Christian Kollmannsberger
Journal: Journal of Clinical Oncology (2006)

primary mediastinal seminoma.This is unlikely to be metastatic disease from the primary mediastinal seminoma, mainly due to the long interval between the diagnosis, and the absence of extracranial lesions.We offer this as additional proof of a genetic predisposition to GCTs, which is congruent with the current data available on the incidence of second primaries in treated testicular cancers.The 15-year actuary risk of a contralateral testis cancer has been reported to be of 2.4% by a Dutch tumor registry. 6 The occurrence of metachronous GCTs is very rare and has been reported in isolated case reports.
Screening Mothers for Intimate Partner Abuse at Well-Baby Care Visits
Authors: Robert S. Thompson, Richard Krugman
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Spontaneous mitral valve prolapse in a breeding colony of rhesus monkeys.
Authors: M M Swindle, J R Blum, S D Lima, J L Weiss
Journal: Circulation (1985)

Mitral valve prolapse was observed in 26 of 92 animals in a harem breeding colony of rhesus monkeys (Macaca mulatta). The affected animals had a systolic murmur best auscultated over the mitral region with the animal in a sitting position. Mid-to-late systolic clicks were also heard. Phonocardiographic examination also demonstrated systolic murmurs and clicks in six of 16 animals. Twenty-three of the animals were studied by M mode and/or two-dimensional echocardiography. The diagnosis was confirmed in 12 animals that had a murmur during the examination. Electrocardiograms revealed T wave abnormalities in five animals and left or right ventricular hypertrophy in five. Four adult animals that died during the course of the study were confirmed at necropsy as having prolapse of the posterior and/or anterior mitral valve leaflets into the atrium. Analysis of the breeding records suggested that mitral valve prolapse was a dominant genetic trait with an approximate birth incidence of 16% to 20% in the colony. The existence of mitral valve prolapse in a nonhuman primate species provides a unique opportunity to study the disease in an experimental animal.
Synuclein-γ Is Closely Involved in Perineural Invasion and Distant Metastasis in Mouse Models and Is a Novel Prognostic Factor in Pancreatic Cancer
Authors: Taizo Hibi, Taisuke Mori, Mariko Fukuma, Ken Yamazaki, Akinori Hashiguchi, Taketo Yamada, Minoru Tanabe, Koichi Aiura, Takao Kawakami, Atsushi Ogiwara, Tomoo Kosuge, Masaki Kitajima, Yuko Kitagawa, Michiie Sakamoto
Journal: Clinical Cancer Research (2009)

Perineural invasion is associated with the high incidence of local recurrence and a dismal prognosis in pancreatic cancer. We previously reported a novel perineural invasion model and distinguished high- and low-perineural invasion groups in pancreatic cancer cell lines. This study aimed to elucidate the molecular mechanism of perineural invasion.To identify key biological markers involved in perineural invasion, differentially expressed molecules were investigated by proteomics and transcriptomics. Synuclein-gamma emerged as the only up-regulated molecule in high-perineural invasion group by both analyses. The clinical significance and the biological property of synuclein-gamma were examined in 62 resected cases of pancreatic cancer and mouse models.Synuclein-gamma overexpression was observed in 38 (61%) cases and correlated with major invasive parameters, including perineural invasion and lymph node metastasis (P < 0.05). Multivariate analyses revealed synuclein-gamma overexpression as the only independent predictor of diminished overall survival [hazard ratio, 3.4 (95% confidence interval, 1.51-7.51)] and the strongest negative indicator of disease-free survival [2.8 (1.26-6.02)]. In mouse perineural invasion and orthotopic transplantation models, stable synuclein-gamma suppression by short hairpin RNA significantly reduced the incidence of perineural invasion (P = 0.009) and liver/lymph node metastasis (P = 0.019 and P = 0.020, respectively) compared with the control.This is the first study to provide in vivo evidence that synuclein-gamma is closely involved in perineural invasion/distant metastasis and is a significant prognostic factor in pancreatic cancer. Synuclein-gamma may serve as a promising molecular target of early diagnosis and anticancer therapy.
Involvement of FLIP in 2-Methoxyestradiol–Induced Tumor Regression in Transgenic Adenocarcinoma of Mouse Prostate Model
Authors: Manonmani Ganapathy, Rita Ghosh, Xie Jianping, Xiaoping Zhang, Roble Bedolla, John Schoolfield, I-Tien Yeh, Dean A. Troyer, Aria F. Olumi, Addanki P. Kumar
Journal: Clinical Cancer Research (2009)

The purpose of this study is to investigate whether Fas-associated death domain interleukin-1 converting enzyme like inhibitory protein (FLIP) inhibition is a therapeutic target associated with 2-methoxyestradiol (2-ME2)-mediated tumor regression.Expression and levels of FLIP were analyzed using (a) real-time PCR and immunoblot analysis in androgen-independent PC-3 cells treated with the newly formulated 2-ME2 and (b) immunohistochemistry in different Gleason pattern human prostate tumors. Transient transfections and chromatin immunoprecipitation (ChIP) assays were used to identify the transcription factors that regulate FLIP. Involvement of FLIP in 2-ME2-induced tumor regression was evaluated in transgenic adenocarcinoma mouse prostate (TRAMP) mice.High Gleason pattern (5+5) human prostate tumors exhibit significant increase in FLIP compared with low Gleason pattern 3+3 (P=or<0.04). 2-ME2 reduced the levels and promoter activity of FLIP (P=0.001) in PC-3 cells. Transient expression assays show sequences between -503/+242 being sufficient for 2-ME2-induced inhibition of FLIP promoter activity. Cotransfection experiments show that overexpression of Sp1 activated, whereas Sp3 inhibited, Sp1 transactivation of FLIP promoter activity (P=0.0001). 2-ME2 treatment reduced binding of Sp1 to the FLIP promoter as evidenced by ChIP. Further, levels of FLIP associated with Fas or FADD decreased, whereas cleavage of caspase-8, levels of Bid, and apoptosis increased in response to 2-ME2 treatment in PC-3 cells. Administration of 2-ME2 regressed established prostate tumors in TRAMP mice that were associated with reduced expression of FLIP and Sp1.Targeting Sp1-mediated FLIP signaling pathway may provide a novel approach for prostate cancer management.
421 COMPARISON OF LIVER STIFFNESS ASSESSMENT BY FIBROSCAN® AND ACOUSTIC RADIATION FORCE IMPULSE IMAGING® FOR THE EVALUATION OF LIVER FIBROSIS AND CIRRHOSIS
Authors: P. Salzl, T. Reiberger, M. Homoncik, B. Payer, B. Schwengerer, M. Peck-Radosavljevic, A. Ferlitsch
Journal: Journal of Hepatology (2010)
Combination therapies with NS5A, NS3 and NS5B inhibitors on different genotypes of hepatitis C virus in human hepatocyte chimeric mice
Authors: Niu Shi, Nobuhiko Hiraga, Michio Imamura, C Nelson Hayes, Yizhou Zhang, Keiichi Kosaka, Akihito Okazaki, Eisuke Murakami, Masataka Tsuge, Hiromi Abe, Hiroshi Aikata, Shoichi Takahashi, Hidenori Ochi, Chise Tateno-Mukaidani, Katsutoshi Yoshizato, Hirotaka Matsui, Akinori Kanai, Toshiya Inaba, Fiona McPhee, Min Gao, Kazuaki Chayama
Journal: Gut (2013)

We recently demonstrated that combination treatment with NS3 protease and NS5B polymerase inhibitors succeeded in eradicating the virus in genotype 1b hepatitis C virus (HCV)-infected mice. In this study, we investigated the effect of combining an NS5A replication complex inhibitor (RCI) with either NS3 protease or NS5B inhibitors on elimination of HCV genotypes 1b, 2a and 2b.The effects of Bristol-Myers Squibb (BMS)-605339 (NS3 protease inhibitor; PI), BMS-788329 (NS5A RCI) and BMS-821095 (NS5B non-nucleoside analogue inhibitor) on HCV genotypes 1b and 2a were examined using subgenomic HCV replicon cells. HCV genotype 1b, 2a or 2b-infected human hepatocyte chimeric mice were also treated with BMS-605339, BMS-788329 or BMS-821095 alone or in combination with two of the drugs for 4 weeks. Genotypic analysis of viral sequences was achieved by direct and ultra-deep sequencing.Anti-HCV effects of BMS-605339 and BMS-821095 were more potent against genotype 1b than against genotype 2a. In in-vivo experiments, viral breakthrough due to the development of a high prevalence of drug-resistant variants was observed in mice treated with BMS-605339, BMS-788329 and BMS-821095 in monotherapy. In contrast to monotherapy, 4 weeks of combination therapy with the NS5A RCI and either NS3 PI or NS5B inhibitor succeeded in completely eradicating the virus in genotype 1b HCV-infected mice. Conversely, these combination therapies failed to eradicate the virus in mice infected with HCV genotypes 2a or 2b.These oral combination therapies may serve as a Peg-alfa-free treatment for patients chronically infected with HCV genotype 1b.
INTRAHEPATIC EXPRESSION OF SERUM HEPATITIS VIRUS-ASSOCIATED ANTIGENS
Authors: Thomas S. Edgington, Donald J. Ritt
Journal: The Journal of Experimental Medicine (1971)

SH virus-associated antigens have been identified in the liver and blood by immunofluorescence. This antigenic expression of the hepatitis agent or its genome is found in the cytoplasm of hepatocytes and other cells of the liver. Acute hepatitis is associated with hepatocellular localization of SH antigen, whereas alternative or additional SH antigen in the cytoplasm of nonhepatocytes is observed in chronic or recurrent hepatitis. Persistent intrahepatic SH antigen has also been observed in conversion from acute to chronic hepatitis, and the persistence of this virus-associated antigen in the liver may serve a significant pathogenetic role in mediating direct anti-tissue responses as well as local immune complex reactions. Competitive inhibition studies of SH antigen suggest at least two antigenically and sterically independent determinants on the SH particle.
Prospective Study of Smoking and the Risk of Breast Cancer
Authors: S. J. London, G. A. Colditz, M. J. Stampfer, W. C. Willett, B. A. Rosner, F. E. Speizer
Journal: JNCI Journal of the National Cancer Institute (1989)

In 1976, 117, 557 women in the United States aged 30–55 years and without a history of cancer provided detailed information on current smoking habits. By 1986, 1,788 cases of breast cancer had been documented during 1,133,682 person-years. There was no association between current smoking and risk of breast cancer (multivariate-adjusted relative risk for smokers of ≥25 cigarettes/day compared to nonsmokers: 1.02, 95% confidence interval, 0.86–1.22). Past smoking also was unrelated to breast cancer risk (relative risk, 1.08; 95% confidence interval, 0.96–1.20). The results did not differ by menopausal status. Tumor size and the presence of nodal metastases were unrelated to smoking. Smoking was weakly associated with estrogen receptor-positive tumors (relative risk for smokers of ≥25 cigarettes/day compared with never smokers, 1.38; 95% confidence interval, 1.04–1.84), but there was no dose-response relationship across categories of current smoking. These results suggest that smoking and breast cancer are not materially related [J Natl Cancer Inst 81:1625–1631, 1989]
D-Dimer, Inflammatory Markers, and Lower Extremity Functioning in Patients With and Without Peripheral Arterial Disease
Authors: Mary McGrae McDermott, Philip Greenland, David Green, Jack M. Guralnik, Michael H. Criqui, Kiang Liu, Cheeling Chan, William H. Pearce, Lloyd Taylor, Paul M Ridker, Joseph R. Schneider, Gary Martin, Nader Rifai, Maureen Quann, Myriam Fornage
Journal: Circulation (2003)

Background— We determined whether higher levels of D-dimer, C-reactive protein (CRP), fibrinogen, and serum amyloid A are associated independently with functional impairment in patients with and without peripheral arterial disease (PAD). Methods and Results— Participants were 370 men and women with PAD (ankle brachial index &lt;0.90) and 231 without PAD. Functional outcomes were 6-minute walk distance and 4-meter walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 (12=best). Adjusting for age, sex, ankle brachial index, comorbidities, and other potential mediators and confounders, D-dimer levels were associated independently and inversely with performance on all 3 functional measures in the entire cohort and among patients with and without PAD, respectively. Adjusting for known and potential confounders, CRP levels were associated independently with 6-minute walk distance and the summary performance score among participants with PAD. No significant associations were observed between CRP and the functional measures among participants without PAD. Fibrinogen and SAA levels were not associated independently with the functional measures. Conclusions— Higher D-dimer levels are associated with poorer functioning among individuals with and without PAD. Higher CRP levels were associated with poorer 6-minute walk performance and a lower summary performance score among participants with PAD but not among those without PAD. Additional study is needed to determine whether D-dimer and CRP are involved in the pathophysiology of functional impairment or whether they are simply sensitive markers of the extent of systemic atherosclerosis.
Chronic cough: from a complex dysfunction of the neurological circuit to the production of persistent cough
Authors: Adalberto Pacheco
Journal: Thorax (2014)

Chronic cough or cough that lasts more than 8 weeks, once a chest x-ray and spirometry are confirmed normal, is caused by an alteration in a section of the route between peripheral receptors, mainly in the upper and lower airway and oesophagus, spinal cord and the cough centre in the brain stem involving the cortex. These mechanisms of cough have their homology in the circuit of chronic pain, and on that basis, should expand future research of chronic cough. Clinically chronic cough is easy to diagnose by an excessive response or hypertussia to low-intensity stimuli or banal stimuli, which we now call hypersensitivity cough syndrome, quantified by a positive reflex cough with capsaicin or citric acid. However, hypersensitivity cough syndrome can be impossible to quantify in the laboratory when the hyper-responsiveness originates in the central nervous system. This is normally caused by excessive peripheral input or convergence of stimuli from different sources. Once central hypersensitivity is acquired, peripheral input is not as important for activation of the cough.
Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia
Authors: Guilherme Augusto dos Santos, Lev Kats, Pier Paolo Pandolfi
Journal: The Journal of Experimental Medicine (2013)

Acute promyelocytic leukemia (APL) is a hematological malignancy driven by a chimeric oncoprotein containing the C terminus of the retinoic acid receptor-a (RARa) fused to an N-terminal partner, most commonly promyelocytic leukemia protein (PML). Mechanistically, PML-RARa acts as a transcriptional repressor of RARa and non-RARa target genes and antagonizes the formation and function of PML nuclear bodies that regulate numerous signaling pathways. The empirical discoveries that PML-RARa–associated APL is sensitive to both all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO), and the subsequent understanding of the mechanisms of action of these drugs, have led to efforts to understand the contribution of molecular events to APL cell differentiation, leukemia-initiating cell (LIC) clearance, and disease eradication in vitro and in vivo. Critically, the mechanistic insights gleaned from these studies have resulted not only in a better understanding of APL itself, but also carry valuable lessons for other malignancies.
Regional distribution of pulmonary ventilation and perfusion in elderly subjects
Authors: J. Holland, J. Milic-Emili, P. T. Macklem, D. V. Bates
Journal: Journal of Clinical Investigation (1968)

Using radioactive xenon, we measured the regional distribution of pulmonary ventilation and blood flow in six normal men, whose ages ranged between 65 and 75 yr. The measurements were made in the standing position. The static volume-pressure relation of the lungs was also measured in five of the subjects. The results indicate that by comparison with normal young men: (a) Blood flow to the upper lung zones was increased, although it still remained predominant in the lower zones. (b) Ventilation distribution during a vital capacity inspiration was similar to that seen in young subjects. (c) In five of the six elderly subjects, however, the distribution of ventilation in the resting tidal volume range was not preferential to the lower zones as it was in young men. This was probably caused by airway closure in the lower lung zones. The elderly subjects thus exhibit during normal tidal volume breathing a ventilation distribution pattern similar to that observed in young subjects when breathing at low lung volumes, i.e., near residual volume. This difference is probably due to the combined effect of the loss in elastic recoil of the lungs observed in the elderly subjects and of a decreased resistance to collapse of the aged airways. These findings suggest that in the elderly subjects there is a significant regional ventilation-perfusion impairment during quiet breathing, which may explain in part the reported increase in alveolar-arterial oxygen difference with advancing age.
Gene Transfer of Human <i>Apoe</i> Isoforms Results in Differential Modulation of Amyloid Deposition and Neurotoxicity in Mouse Brain
Authors: Eloise Hudry, Jonathan Dashkoff, Alysson D. Roe, Shuko Takeda, Robert M. Koffie, Tadafumi Hashimoto, Maria Scheel, Tara Spires-Jones, Michal Arbel-Ornath, Rebecca Betensky, Beverly L. Davidson, Bradley T. Hyman
Journal: Science Translational Medicine (2013)

Introduction of different APOE isoforms modulates Aβ peptide aggregation and neurotoxicity after amyloid deposition in mouse brain.