tbuckley/cabot-search huggingface dataset:
The endogenous vascular elastase that governs development and progression of monocrotaline-induced pulmonary hypertension in rats is a novel enzyme related to the serine proteinase adipsin.
Authors: L Zhu, D Wigle, A Hinek, J Kobayashi, C Ye, M Zuker, H Dodo, F W Keeley, M Rabinovitch
Journal: Journal of Clinical Investigation (1994)

We showed previously a cause and effect relationship be- tween increased activity of an endogenous vascular elastase (EVE) and experimentally induced pulmonary hyperten- sion in rats.We now report the isolation and characterization of EVE.Degenerate oligonucleotides synthesized to ho- mologous sequences in serine elastases were used in a PCR with rat pulmonary artery (PA) cDNA.The PCR product hybridized to a 1.2-kb mRNA and the intensity of hybridiza- tion was threefold increased in RNA from rat hypertensive PA at a timepoint when EVE activity was increased.The PCR product was used to screen a cDNA library and se- quences obtained encoded rat adipsin.We then used immunoaffinity to purify EVE.An antibody to the elastin-binding protein was used to remove this competitor of elastase from the PA extract and the elastolytic activity increased 100- fold.The enzyme was purified using an antibody that recog- nizes NH2-terminal sequences of serine proteinases and the eluate was further purified using an antibody raised against recombinant adipsin.A single band at 20 kD immunoreac- tive with the adipsin antibody was resolved as an active enzyme on an elastin substrate gel.Immunogold labeling with an antibody to an adipsin peptide sequence localized EVE to PA smooth muscle cells.This is the first isolation of EVE; it appears to be a novel enzyme related to the serine proteinase adipsin originally found in adipose tissue.(
Ambient particle inhalation and the cardiovascular system: potential mechanisms.
Authors: K Donaldson, V Stone, A Seaton, W MacNee
Journal: Environmental Health Perspectives (2001)

Well-documented air pollution episodes throughout recent history have led to deaths among individuals with cardiovascular and respiratory disease. Although the components of air pollution that cause the adverse health effects in these individuals are unknown, a small proportion by mass but a large proportion by number of the ambient air particles are ultrafine, i.e., less than 100 nm in diameter. This ultrafine component of particulate matter with a mass median aerodynamic diameter less than 10 microm (PM(10) may mediate some of the adverse health effects reported in epidemiologic studies and for which there is toxicologic evidence to support this contention. The exact mechanism by which ultrafine particles have adverse effects is unknown, but these particles have recently been shown to enhance calcium influx on contact with macrophages. Oxidative stress is also to be anticipated at the huge particle surface; this can be augmented by oxidants generated by recruited inflammatory leukocytes. Atheromatous plaques form in the coronary arteries and are major causes of morbidity and death associated epidemiologically with particulate air pollution. In populations exposed to air pollution episodes, blood viscosity, fibrinogen, and C-reactive protein (CRP) were higher. More recently, increases in heart rate in response to rising air pollution have been described and are most marked in individuals who have high blood viscosity. In our study of elderly individuals, there were significant rises in CRP, an index of inflammation. In this present review, we consider the likely interactions between the ultrafine particles the acute phase response and cardiovascular disease.
Physiologic systemic iron metabolism in mice deficient for duodenal Hfe
Authors: Maja Vujic Spasic, Judit Kiss, Thomas Herrmann, Regina Kessler, Jens Stolte, Bruno Galy, Birgit Rathkolb, Eckhard Wolf, Wolfgang Stremmel, Matthias W. Hentze, Martina U. Muckenthaler
Journal: Blood (2007)
Weekend Activities and Respiratory Illness
Authors: Alfons Salinger
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The Tecumseh Study of acute respiratory illness in an American community, by Monto and Ulman (227:164, 1974), showed that on Fridays, Saturdays, and Sundays, the frequency of illness onsets increased, reaching a peak on Mondays, mainly in 5- to 19-year-olds. This proves an observation I and probably many other physicians have made through the years in private practice in a larger city. I cannot share, though, the authors' conclusions about the main factors that might be responsible. It was always my impression that the main contributing factor was physical exhaustion brought on by unaccustomed activities in which this age group indulged on weekends: late hours due to the endless viewing of TV, social activities extending into the night, physical exhaustion caused by participating in strenuous exercises leading to overexertion, irregularly served less-balanced meals, and possibly overindulgence in eating and drinking of unaccustomed items. Whenever I observed the prevalence
Computer system for assisting with clinical interpretation of tumour marker data.
Authors: M. S. Leaning, S. Gallivan, E. S. Newlands, J. Dent, M. Brampton, D. B. Smith, K. D. Bagshawe
Journal: BMJ (1992)

OBJECTIVE--To design and evaluate a computer advisory system for the treatment of gestational trophoblastic tumour. DESIGN--A comparison of clinicians9 treatment decisions with those of the computer system. Two datasets were used: one to calibrate the system and one to independently evaluate it. SETTING--Department of medical oncology. PATIENTS--Computerised records of 290 patients with low risk gestational trophoblastic tumour for whom the advisory system could predict the adequacy of treatment. The calibration set comprised patients admitted during 1979-86(227) and the test set patients during 1986-89(63). MAIN OUTCOME MEASURES--The system9s accuracy in predicting need to change treatment compared with clinicians9 actions. The mean time faster that the system was in predicting the need to change treatment. RESULTS--On the calibration dataset the system was 94% (164/174) accurate in predicting patients whose treatment was adequate, recommending change when none occurred in only 10 (6%) patients. In patients whose treatment was changed the system recommended change earlier than clinicians in 39/53 cases (74%), with a mean time advantage of 14.9 (SE 2.02) days. On the test dataset the system had an accuracy of 91% (31/34) in predicting treatment adequacy and a false positive rate of 9% (3/34). The system recommended change earlier than clinicians in 22/29 cases (76%), with a mean time advantage of 12.5 (2.22) days. CONCLUSIONS--The computer advisory system could improve patient management by reducing the time spent receiving ineffective treatment. This has implications for both patient time and clinical costs.
Histone Deacetylase Inhibitor Trichostatin A Represses Estrogen Receptor α-Dependent Transcription and Promotes Proteasomal Degradation of Cyclin D1 in Human Breast Carcinoma Cell Lines
Authors: John Patrick Alao, Eric W-F. Lam, Simak Ali, Laki Buluwela, Walter Bordogna, Peter Lockey, Rana Varshochi, Alexandra V. Stavropoulou, R. Charles Coombes, David M. Vigushin
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Estrogen receptor α (ERα)-positive breast cancer cell lines are up to 10 times more sensitive than ERα-negative cell lines to the antiproliferative activity of the histone deacetylase inhibitor trichostatin A (TSA). The purpose of the study was to investigate the mechanisms underlying this differential response. Experimental Design and Results: In the ERα-positive MCF-7 cell line, TSA repressed ERα and cyclin D1 transcription and induced ubiquitin dependent proteasomal degradation of cyclin D1, leading primarily to G1-S-phase cell cycle arrest. By contrast, cyclin D1 degradation was enhanced but its transcription unaffected by TSA in the ERα-negative MDA-MB-231 cell line, which arrested in G2-M phase. Cyclin D1 degradation involved Skp2/p45, a regulatory component of the Skp1/Cullin/F-box complex; silencing SKP2 gene expression by RNA interference stabilized cyclin D1 and abrogated the cyclin D1 down-regulation response to TSA. Conclusions: Tamoxifen has been shown to inhibit ERα-mediated cyclin D1 transcription, and acquired resistance to tamoxifen is associated with a shift to ERα-independent cyclin D1 up-regulation. Taken together, our data show that TSA effectively induces cyclin D1 down-regulation through both ERα-dependent and ERα-independent mechanisms, providing an important new strategy for combating resistance to antiestrogens.
Abstract 1534: CD163-expressing macrophages constitute a distinct malignancy-promoting phenotype in melanoma facilitating tumor development, progression, and metastasis: Implications for novel anticancer therapy.
Authors: Maciej B. Maniecki, Anders Etzerodt, William E. Damsky, Aisha Rafique, David Gonzalez, Lars Dyrskjøt, Holger J. Møller, Marcus W. Bosenberg, Søren K. Moestrup
Journal: Cancer Research (2013)

Abstract Tumor-infiltrating macrophages are recruited to the tumor microenvironment and believed to play a key role in tumor development, progression, and metastasis by producing growth factors and promoting neoangiogenesis. Here, we show that CD163-expressing macrophages express a distinct gene expression signature capable of facilitating tumor development and progression. This supports our earlier findings showing significant correlation between CD163+ macrophage density, tumor grade, and poor prognosis in patients with melanoma. Selective eradication of CD163-expressing tumor-associated macrophages through receptor-mediated delivery of nanoparticles encapsulating the cytotoxic agent doxorubicin significantly inhibited tumor formation and prolonged survival in an immune-competent conditional mouse model of BrafV600E-induced, Pten-deficient metastatic melanoma. High-resolution dynamic intravital imaging showed specific targeting of a subpopulation of tumor-infiltrating macrophages expressing the scavenger receptor CD163, including Tie2-expressing macrophages recently identified as being highly proangiogenic. In conclusion, our findings identify CD163-expressing macrophages as a distinct malignancy-promoting phenotype and indicate a novel therapeutic target in cancer. Citation Format: Maciej B. Maniecki, Anders Etzerodt, William E. Damsky Jr., Aisha Rafique, David Gonzalez, Lars Dyrskjøt, Holger J. Møller, Marcus W. Bosenberg, Søren K. Moestrup. CD163-expressing macrophages constitute a distinct malignancy-promoting phenotype in melanoma facilitating tumor development, progression, and metastasis: Implications for novel anticancer therapy. [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 1534. doi:10.1158/1538-7445.AM2013-1534
Influenza — 1918, a Revisit?
Authors: Louis Weinstein
Journal: New England Journal of Medicine (1976)

The recent recommendation by the President of the United States that a vaccine containing swine-influenza virus be promptly prepared for mass immunization in the early fall of 1976 was stimulated by the experience at Fort Dix, New Jersey, where, within the last two months, this agent was identified as the cause of disease that led to one death. Transmission from person to person was documented. This fact alone would not have provoked a strong reaction were it not for the suspicion that this was the agent that had probably been responsible for the pandemic of 1918. The basis for this . . .
4-Oxo-Fenretinide, a Recently Identified Fenretinide Metabolite, Induces Marked G2-M Cell Cycle Arrest and Apoptosis in Fenretinide-Sensitive and Fenretinide-Resistant Cell Lines
Authors: Maria Grazia Villani, Valentina Appierto, Elena Cavadini, Arianna Bettiga, Alessandro Prinetti, Margaret Clagett-Dame, Robert W. Curley, Franca Formelli
Journal: Cancer Research (2006)

Abstract 4-Oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) is a recently identified metabolite of fenretinide (4-HPR). We explored the effectiveness of 4-oxo-4-HPR in inducing cell growth inhibition in ovarian, breast, and neuroblastoma tumor cell lines; moreover, we investigated the molecular events mediating this effect in two ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780/HPR) to 4-HPR. 4-Oxo-4-HPR was two to four times more effective than 4-HPR in most cell lines, was effective in both 4-HPR–sensitive and 4-HPR–resistant cells, and, in combination with 4-HPR, caused a synergistic effect. The tumor growth-inhibitory effects of 4-oxo-4-HPR seem to be independent of nuclear retinoid receptors (RAR), as indicated by the failure of RAR antagonists to inhibit its effects and by its poor ability to bind and transactivate RARs. Unlike 4-HPR, which only slightly affected the G1 phase of the cell cycle, 4-oxo-4-HPR caused a marked accumulation of cells in G2-M. This effect was associated with a reduction in the expression of regulatory proteins of G2-M (cyclin-dependent kinase 1 and cdc25c) and S (cyclin A) phases, and with an increase in the expression of apoptosis-related proteins, such as p53 and p21. Apoptosis was induced by 4-oxo-4-HPR in both 4-HPR–sensitive and 4-HPR–resistant cells and involved activation of caspase-3 and caspase-9 but not caspase-8. We also showed that 4-oxo-4-HPR, similarly to 4-HPR, increased reactive oxygen species generation and ceramide levels by de novo synthesis. In conclusion, 4-oxo-4-HPR is an effective 4-HPR metabolite that might act as therapeutic agent per se and, when combined with 4-HPR, might improve 4-HPR activity or overcome 4-HPR resistance. (Cancer Res 2006; 66(6): 3238-47)
Comparison of Low-Intensity Warfarin Therapy with Conventional-Intensity Warfarin Therapy for Long-Term Prevention of Recurrent Venous Thromboembolism
Authors: Clive Kearon, Jeffrey S. Ginsberg, Michael J. Kovacs, David R. Anderson, Philip Wells, Jim A. Julian, Betsy MacKinnon, Jeffrey I. Weitz, Mark A. Crowther, Sean Dolan, Alexander G. Turpie, William Geerts, Susan Solymoss, Paul van Nguyen, Christine Demers, Susan R. Kahn, Jeannine Kassis, Marc Rodger, Julie Hambleton, Michael Gent
Journal: New England Journal of Medicine (2003)

Warfarin is very effective in preventing recurrent venous thromboembolism but is also associated with a substantial risk of bleeding. After three months of conventional warfarin therapy, a lower dose of anticoagulant medication may result in less bleeding and still prevent recurrent venous thromboembolism.
Bilirubin Diglucuronide Formation in Intact Rats and in Isolated Gunn Rat Liver
Authors: J. Roy Chowdhury, N. Roy Chowdhury, Ulrich Gärtner, Allan W. Wolkoff, Irwin M. Arias
Journal: Journal of Clinical Investigation (1982)

Bilirubin diglucuronide (BDG) may be formed in vitro by microsomal UDP glucuronosyl transferase (EC 2.4.1.17)-mediated transfer of a second mole of glucuronic acid from UDP-glucuronic acid, or by dismutation of bilirubin monoglucuronide (BMG) to BDG and unconjugated bilirubin, catalyzed by an enzyme (EC 2.4.1.95) that is concentrated in plasma membrane-enriched fractions of rat liver. To evaluate the role of these two enzymatic mechanisms in vivo, [3H]bilirubin mono-[14C]glucuronide was biosynthesized, purified by thin-layer chromatography, and tracer doses were infused intravenously in homozygous Gunn (UDP glucuronyl transferase-deficient) rats or Wistar rats. Bilirubin conjugates in bile were separated by high-pressure liquid chromatography and 3H and 14C were quantitated. In Gunn rats, the 14C:3H ratio in BDG excreted in bile was twice the ratio in injected BMG. In Wistar rats the 14C:3H ratio in biliary BDG was 1.25 ± 0.06 (mean ± SEM) times the ratio in injected BMG. When double labeled BMG was injected in Wistar rats after injection of excess unlabeled unconjugated bilirubin (1.7 μmol), the 14C:3H ratio in BDG excreted in bile was identical to the ratio in injected BMG. Analysis of isomeric composition of bilirubin conjugates after alkaline hydrolysis or alkaline methanolysis indicated that the bile pigments retained the IXα configuration during these experiments. The results indicate that both enzymatic dismutation and UDP glucuronyl transferase function in vivo in BDG formation, and that dismutation is inhibited by a high intrahepatic concentration of unconjugated bilirubin. This hypothesis was supported by infusion of [3H]bilirubin-monoglucuronide in isolated perfused homozygous Gunn rat liver after depletion of intrahepatic bilirubin by perfusion with bovine serum albumin (2.5%), and after bilirubin repletion following perfusion with 0.34 mM bilirubin. From 20 to 25% of injected radioactivity was recovered in BDG in bile in the bilirubin-depleted state; only 8-10% of radioactivity was in BDG in bile after bilirubin repletion.
The Expanding Spectrum of Behçet Syndrome
Authors: Emin Kansu
Journal: JAMA (1977)

BEHÇET syndrome was originally characterized by a diagnostic triad of aphthous stomatitis, genital ulceration, and uveitis. However, the spectrum of this entity has progressively broadened with the recognition of multiple organ system involvement; most frequently, dermal vasculitis and arthritis occur. Other manifestations that occur less commonly include CNS involvement, colitis, phlebitis, and myocarditis.<sup>1</sup>We report a case of Behçet syndrome with aphthous stomatitis, genital ulceration, polyarthritis, myocarditis, and severe renal involvement with focal necrotizing glomerulonephritis. To our knowledge, it represents the first case of acute glomerulonephritis as a manifestation of Behçet syndrome <h3>Report of a Case</h3> A 58-year-old man was admitted to Thomas Jefferson University Hospital because of pain in multiple proximal interphalangeal joints and shortness of breath. Since 1967, he had had recurrent aphthous mouth ulcers, intermittent painful swelling of both ankles and the right great toe, and exertional breathlessness. The patient was dyspneic, and his jugular veins
Albert Schweitzer: Physician, Philosopher, Theologian, Musician
Authors: Dana L. Farnsworth
Journal: New England Journal of Medicine (1952)

MANY physicians have carved out distinguished careers in other fields than medicine after having acquired their basic medical training. It remains for a very few persons to enter medicine after major success in another profession. Yet Albert Schweitzer did this, not after success in one activity, but after he had earned doctorates and world-wide reputations in three quite dissimilar fields — philosophy, theology and music. He began his medical studies in 1905 at the age of thirty, pursued them under conditions that would have moved most medical students to give up in despair, and went on to establish a hospital . . .
TCT-489 Comparison Of Arterial, Surrounding Soft Tissue And Nerve Damage With Irrigated Vs. Non-irrigated Radiofrequency Ablation
Authors: Kenichi Sakakura, Elena Ladich, Kristine Fuimaono, Debby Grunewald, Patrick O'Fallon, Fumiyuki Otsuka, Kazuyuki Yahagi, Frank D. Kolodgie, Renu Virmani
Journal: Journal of the American College of Cardiology (2013)
Relationship Between Quantitated Precordial Movement and Left Ventricular Function
Authors: GEORGE C. SUTTON, TAYLOR A. PREWITT, ERNEST CRAIGE
Journal: Circulation (1970)

The relationship between external records of precordial movement and ventricular function has been studied in 61 patients with various cardiac disorders by comparing the records of the apical impulse to the left ventricular volume. A significant correlation between external recordings and the volume data was found in patients with normal or increased ventricular volumes: Patients with a normal record in systole usually had normal end-diastolic and left ventricular stroke volumes; those with a hyperdynamic record in systole usually had an appropriate increase in stroke volume for increased end-diastolic volume; and those with sustained records usually had an increased end-diastolic volume without an appropriate increase in stroke volume, indicating poor myocardial function. Patients with a pressure-loaded left ventricle usually had a sustained record, but this appeared to be related to factors other than volume. These studies demonstrate that records of the apical impulse may provide useful information about left ventricular function.
Aluminium hydroxide granulomas: light and electron microscopic studies and X-ray microanalysis
Authors: D.N. SLATER, J.C.E. UNDERWOOD, T.E. DURRANT, T. GRAY, I.P. HOPPER
Journal: British Journal of Dermatology (1982)

Three children are described in whom painful subcutaneous nodules developed 1–2 years after the injection of adsorbed diphtheria, tetanus and pertussis vaccine. The diagnosis of aluminium hydroxide granuloma was established by ultrastructural examination with X-ray microanalysis.
Effect of using protocols on medical care: randomised trial of three methods of taking an antenatal history.
Authors: R. J. Lilford, M. Kelly, A. Baines, S. Cameron, M. Cave, K. Guthrie, J. Thornton
Journal: BMJ (1992)

OBJECTIVE--To compare the effectiveness of three methods of taking an antenatal history on the quality of obstetric care. DESIGN--Randomised controlled trial. SETTING--Antenatal clinic of St James9s University Hospital, Leeds. SUBJECTS--2424 women attending the hospital for the first (booking) visit. INTERVENTIONS--Histories were taken by midwives using an unstructured paper questionnaire, a structured paper questionnaire (incorporating a checklist), or an interactive computerised questionnaire (incorporating 101 clinical reminders). MAIN OUTCOME MEASURES--The number of clinical responses to factors arising from the antenatal booking history according to method of taking the history. Actions were categorised as medical and surgical, obstetric, personal, current symptoms and treatment, related to maternal age, and related to two common actions (cervical smear testing and dental hygiene) and were weighted for clinical importance by 10 obstetricians. RESULTS--Overall the unstructured questionnaire generated 1063 actions, the structured questionnaire 1146, and the computerised questionnaire 1122. The clinical importance of these actions was lowest for the unstructured questionnaire (overall total value score 1987 v 2182 and 2110 for the structured and computerised questionnaires respectively). The structured questionnaire was better than the computerised questionnaire in the medical and surgical (total value score 191 v 184), obstetric (275 v 241), and personal (430 v 360) categories but inferior in the current symptoms category (179 v 191). CONCLUSION--Structured questionnaires (computerised or paper) provide more and better information, and their use improves clinical response to risk factors. Computerised systems offer no further advantage in antenatal clinics.
Cecil Wilfred Dickens Lewis
Authors: Wilma F Grant
Journal: BMJ (2006)

​FoundationFoundation professor Universities of Western Australia, Auckland, and Hong Kong (b 1916; q Welsh National School of Medicine 1939; FRCS, MCh), died from cerebrovascular disease on 19 March 2006.



Figure 1



Cecil Lewis greatly influenced medical education in Western Australia, New Zealand, and Hong Kong. After service in the Royal Naval Volunteer Reserve during 1940-6, he progressed to senior lecturer in surgery and consultant in surgery at Cardiff United Hospitals. In 1956 he was appointed foundation professor of surgery, University of Western Australia, a chair he occupied for nine years. In 1965 when the University of Auckland was looking for a foundation dean to set up New Zealand's second medical school he took up the challenge. He left after the first class, of 1968, graduated to become foundation professor and director of postgraduate medical education in the University of Hong Kong until 1978. He leaves a second wife, Helen, and three children.