tbuckley/cabot-search huggingface dataset:
Evidence of an Endogenous Digitalis-like Factor in the Plasma of Patients with Acromegaly
Authors: G. Deray, M. Rieu, M.A. Devynck, M.G. Pernollet, P. Chanson, J.P. Luton, P. Meyer
Journal: New England Journal of Medicine (1987)

Evidence suggests that plasma-volume expansion leads to the release of a digitalis-like factor, which is thought to act on the renal tubular cells and cause natriuresis. We postulated that this factor might be present in patients with acromegaly (in whom plasma volume is elevated) and might return to normal levels when the disease was treated successfully. We measured the ability of plasma extracts from patients with acromegaly to inhibit the binding of ouabain to the sodium pump in normal red cells and to inhibit the enzymatic activity (sodium-potassium-ATPase) of the sodium pump in membrane preparations from normal kidneys. In 21 patients with active acromegaly, the mean (+/- SE) level of ouabain-binding inhibition (1.56 +/- 0.38) was higher (P less than 0.01) than that in either 11 successfully treated patients (0.18 +/- 0.05) or in 27 normal controls (0.19 +/- 0.03). The inhibition of sodium-potassium-ATPase activity by plasma was also greater in patients with active acromegaly (38.1 +/- 6.8 percent) than in successfully treated patients (18.4 +/- 5.6 percent, P less than 0.05) or controls (21.1 +/- 2.7 percent, P less than 0.05). Significant correlations were found between plasma volume and ouabain-binding inhibition in 23 patients (r = 0.72, P less than 0.01) and sodium-potassium-ATPase inhibition in 19 patients (r = 0.62, P less than 0.01). Pituitary adenomectomy decreased plasma volume and the inhibition by plasma of ouabain binding. We conclude that an endogenous digitalis-like factor is present in the plasma of patients with chronic volume expansion due to acromegaly. These results are consistent with the hypothesis that this natriuretic factor may have a physiologic role in water and sodium homeostasis.
Phenistix urine test-strip and desferioxamine.
Authors: H V Finlay
Journal: BMJ (1978)

the embryonic circulatory system has developed interchange of transplantation antigens is possible; before this some traffic of trophoblastic cells or of subcellular material from the fetal complex to the mother may occur, while the passage of immunopotent substances into the embryo from the maternal circulation is also a possibility.Antigen thus transferred could be not only non-sensitising in form and amount but also capable of defunctioning rejection mechanisms in ways previously reviewed' and artificially explored.6Whichever of these hypothetical mechanisms may be shared with the cancer-host and the surgical transplant-recipient systems, it seems clear that the immunological equilibrium existing throughout pregnancy is a dynamic multifactorial system with a steady interchange of immune information and a concominant ever-changing series of reactions.Knowledge of the kinetics of humoral and cellular responses to the two-way traffic in trans- plantation antigens is the central need of further understanding.
Ethical Challenges of Preexposure Prophylaxis for HIV
Authors: Jonathan S. Jay, Lawrence O. Gostin
Journal: JAMA (2012)

EMTRICITABINE/TENOFOVIR (Truvada; Gilead Sciences) became the first drug approved by the US Food and Drug Administration (FDA) for preexposure prophylaxis (PrEP) of human immunodeficiency virus (HIV) for adults at high risk.Clinical trials have demonstrated that daily use of oral antiretroviral drugs can reduce the risk of HIV acquisition through sexual intercourse.With 50 000 new HIV infections per year in the United States 1 and 2 million per year worldwide, 2 PrEP could become a major component of "combination prevention" along with condoms, counseling, testing, and treatment.
Toll-like receptor 4 and myeloid differentiation factor 88 provide mechanistic insights into the cause and effects of interleukin-6 activation in mouse liver regeneration
Authors: Javier Vaquero, Jean S. Campbell, Jamil Haque, Ryan S. McMahon, Kimberly J. Riehle, Renay L. Bauer, Nelson Fausto
Journal: Hepatology (2011)

Partial hepatectomy (PH) consistently results in an early increase of circulating interleukin-6 (IL-6), which is thought to play a major role in liver regeneration. Activation of this cytokine after PH requires the adaptor protein, MyD88, but the specific MyD88-related receptors involved remain unidentified. It is also unknown whether the magnitude of IL-6 elevation determines the extent of subsequent hepatocyte proliferation. Here, we uncovered artifacts in the assessment of circulating IL-6 levels when using cardiac puncture in mice after PH. By using retro-orbital bleed sampling, we show that the circulating levels of IL-6 after PH were not directly correlated with the extent of hepatocyte DNA synthesis in individual mice. The IL-6 increase after PH was attenuated in all lipopolysaccharide-hyporesponsive mouse strains studied (e.g., C3H/HeJ, Tlr4 null, Cd14 null, Tlr2,4,9 null, and Tlr2,4-Caspase1 null) and was severely abrogated in Myd88 null mice. Despite attenuated IL-6 levels, Tlr4 null mice showed normal signaling downstream of IL-6 and normal hepatocyte proliferation. In contrast, Myd88 null mice showed severe impairments in signal transducer and activator of transcription 3 phosphorylation and Socs3 induction, but had enhanced and prolonged extracellular signal-related kinase 1 and 2 phosphorylation in the first 6 hours after PH. Unexpectedly, these changes were associated with accelerated initiation of hepatocyte proliferation, as assessed by hepatocyte bromodeoxyuridine incorporation, phospho-histone H3 immunostaining, and cyclin E and A protein expression. Conclusion: TLR-4 signaling contributes to IL-6 activation after PH, but the Tlr4 -independent component appears sufficient for ensuring intact signaling downstream of IL-6. The lack of correlation between IL-6 levels and hepatocyte proliferation after PH, and the accelerated start of hepatocyte proliferation in Myd88 null mice despite abrogated cytokine activation, may highlight relevant antiproliferative effects of IL-6 signaling, possibly via Socs3 , in the regulation of liver regeneration. (Hepatology 2011;)
Normal Blood Supply to the Human His Bundle and Proximal Bundle Branches
Authors: RICHARD J. FRINK, THOMAS N. JAMES
Journal: Circulation (1973)

The three major coronary arteries of 10 normal human hearts were injected with differentially colored gelatin mass for histologic determination of the blood supply to the His bundle and proximal bundle branches. The His bundle was dually supplied by the A-V node artery and the first septal branch of the left anterior descending artery in nine hearts, but entirely by the A-V node artery in one. The proximal right bundle branch was supplied by both the A-V node artery and septal branch in five hearts, only the septal branch in four, and the A-V node artery alone in one. The anterior half of the left bundle branch was dually supplied by the A-V node artery and septal branch in four hearts, entirely by the septal branch in five, and the A-V node artery alone in one. The posterior half of the left bundle branch was supplied by the A-V node artery alone in five hearts, dually by the A-V node artery and septal branch in four, and by the septal branch alone in one. The blood supply to most of the human His bundle and its proximal branches is thus dual in origin, with anastomosis principally within the His bundle.
ABC of sexual health: Female sexual problems I: Loss of desire---what about the fun?
Authors: J. Butcher
Journal: BMJ (1999)

Loss of desire for sexual activity is the commonest presenting

female sexual dysfunction and often the hardest to treat. Whether this loss of sexual desire should be seen as abnormal or simply as a variation of normal has long been debated. Much literature is available on female loss of desire, considering sexuality for women from various angles. The American PsychiatricAssociation's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), which gives our working classification of psychosexual dysfunction, would classify it as hypoactive sexual desire disorder and sexual aversion disorder.

Masters and Johnson's original “human sexual response curve” helps us to understand loss of desire in the context of the normal sexual response. This diagrammatic representation describes increasing sexual pleasure against time —(desire for sexual activity followed by arousal, orgasm, and finally resolution. It is important to remember, however, that the physiologies of desire, arousal, and orgasm are separate entities and therefore are not dependent on each other. Women with loss of desire (hypoactive sexual desire disorder) can have good sexual functioning. In essence, they will not initiate sexual contact.



The normal female sexual response. (Adapted from Masters WH, Johnson VE. Human sexual response. Boston, MA: Little, Brown, 1966)



Is desire a thought or a feeling? The answer is not clear, and, certainly early in loving relationships, physical arousal closely follows any sexual thought. Initially, we have a sexual thought, which then facilitates the arousal mechanism through neurological pathways. The thought could be anticipation of the evening ahead or a memory of a previous sexual encounter. Women who do not desire sexual activity can operate quite well sexually once engaged in the sexual encounter. Touch around the clitoris and genital area facilitates neurological pathways, producing good arousal, good lubrication, and on to orgasm.

Much research into sexual desire is being undertaken, but …
Promise of retrial for Bahraini doctors was for Western eyes only
Authors: S. Arie, M. Houston
Journal: BMJ (2011)

The 20 health professionals in Bahrain who were given long jail sentences by a military court for alleged antigovernment activity will not get a full retrial, despite an announcement last week that calmed international concerns, a lawyer representing one of the accused has said.

Bahrain’s attorney general, Ali Alboainain, announced on 5 October that the 20, who were accused of attempting to topple the regime while treating injured political protesters earlier this year, should be “retried before the ordinary courts” after an international outcry over the sentences of between five and 15 years handed down at the end of September ( BMJ 2011;343:d6475, doi:10.1136/bmj.d6475).

“By virtue of the retrials, the accused will have the benefit of full re-evaluation of evidence and full opportunity to present their defence,” …
Abstract 4838: Upregulation of ERBB3/HER3 by FOXD3, an adaptive response promoting resistance to RAF/MEK-inhibitors
Authors: Ethan V. Abel, Kevin J. Basile, Andrew E. Aplin
Journal: Cancer Research (2012)

Abstract Targeting the B-RAF/MEK/ERK pathway has shown promise in the treatment of mutant B-RAF melanomas, but resistance to RAF/MEK-inhibitors has been observed. We have previously shown that the stem cell transcription factor FOXD3 is upregulated in mutant B-RAF melanoma cells upon RAF/MEK-inhibition, but the consequences of FOXD3 upregulation are unclear. Using microarrays and ChIP-sequencing, we identified ERBB3/HER3 as a direct target of FOXD3. FOXD3 enhanced ERBB3 expression and responsiveness to its ligand neuregulin-1 (NRG1). Interestingly, PLX4032 or AZD6244-treated cells displayed enhanced NRG1-dependent ERBB3 phosphorylation and downstream AKT activation. These effects were associated with NRG1 enhanced migration and growth of RAF/MEK-inhibitor treated cells in vitro. Phosphorylation of ERBB3 was found to be dependent on ERBB2/HER2, as NRG1/ERBB3-signaling was inhibited by ERBB2-targeting siRNA, the ERBB2-blocking antibody trastuzumab and the ERBB2-inhibitor lapatinib. Additionally, the combination of lapatinib and PLX4032 was more effective than either alone at inhibiting colony formation in the presence or absence of NRG1. Similarly, we found that combining lapatinib with PLX4720 was more effective than either drug alone at reducing tumor burden in melanoma xenografts. These results suggest that upregulation of ERBB3 by FOXD3 serves as an adaptive response to protect melanoma cells from the effects of RAF/MEK-inhibitors and promotes resistance. In summary, targeting the NRG1/ERBB3 pathway in conjunction with RAF/MEK may provide a clinical benefit. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4838. doi:1538-7445.AM2012-4838
Potential involvement of Notch1 signalling in the pathogenesis of primary cutaneous CD30-positive lymphoproliferative disorders
Authors: M.R. Kamstrup, E. Ralfkiaer, G.L. Skovgaard, R. Gniadecki
Journal: British Journal of Dermatology (2008)

The central role of Notch signalling in T-cell development and oncogenesis raises the question of the importance of this pathway in cutaneous T-cell lymphomas.To investigate the pattern of expression of Notch and its ligands, Jagged and Delta, in skin samples of primary cutaneous CD30+ lymphoproliferative disorders.Immunohistochemistry of formalin-fixed, paraffin-embedded skin samples from 12 patients with lymphomatoid papulosis (LyP) and 11 patients with primary cutaneous anaplastic large cell lymphoma (ALCL). Immunofluorescence studies of fresh skin samples obtained from three patients with LyP and two patients with primary cutaneous ALCL.We identified single Notch1-positive cells or small clusters of atypical cells in LyP. Similarly, strongly positive Jagged1 cells tended to be localized in clusters. Primary cutaneous ALCL had higher expression of Notch1 and Jagged1 compared with LyP. Cells expressing Notch1 and Jagged1 were colocalized and a subset of cells expressed both the receptor and the ligand. The expression of the ligand Delta1 was low to undetectable in both types of lymphoproliferations. A subpopulation of lymphoma cells was found to coexpress Notch1 and activated Akt kinase.These results imply a potential role for the Notch signalling pathway in the pathogenesis of primary cutaneous CD30+ lymphoproliferative disorders and provide a rationale for the exploration of the activity of Notch antagonists in the therapy of these diseases.
An Outbreak of Streptococcus pyogenes Infections in a Nursing Home
Authors: FREDERICK L. RUBEN
Journal: Annals of Internal Medicine (1984)

An outbreak of serious infections caused by Streptococcus pyogenes occurred in a nursing home for elderly patients. The outbreak began in mid-winter and continued for 12 months. Thirteen residents and two nurses had infections. Severity of infection was worse in residents, who developed sepsis, necrotizing fasciitis, cellulitis, septic arthritis, pneumonia, and conjunctivitis; in contrast, the nurses had pharyngitis only. Six of thirteen residents required acute hospital care, and the index case died with sepsis. Typing of S. pyogenes was done in 13 of 15 cases, and the same serotype (M-non-typable, T-25) was found. Control measures consisted of identifying all patients with infections, obtaining cultures, and providing prompt treatment. Patients in nursing homes are highly susceptible to serious infections with S. pyogenes.
SEQUENTIAL ANALYSIS OF CONSECUTIVE PATIENTS OVER 13 MONTHS TO DETERMINE RELATIONSHIP OF DISEASE SEVERITY AND TECHNICAL PERFORMANCE TO OUTCOMES IN CONGENITAL CARDIAC SURGERY.
Authors: Meena Nathan, Hua Liu, Pedro J. del Nido, John E. Mayer, Francis Fynn-Thompson, Emile A. Bacha, Frank A. Pigula
Journal: Journal of the American College of Cardiology (2011)
N Terminal pro-Brain Natriuretic Peptide Level is Associated with SYNTAX Score and Aortic Distensibility in Patients with Stable Coronary Artery Disease
Authors: Durmuş Yıldıray Şahin, Mustafa Gür, Zafer Elbasan, Nermin Yıldız Koyunsever, Caner Türkoğlu, Selahattin Akyol, Arafat Yıldırım, Gökhan Gözübüyük, Betül Özaltun, Murat Çaylı
Journal: Journal of the American College of Cardiology (2013)
A NEW PREPARALYTIC SYMPTOM OF POLIOMYELITIS
Authors: JOHN ADAMS COLLIVER
Journal: JAMA (1913)

"Infantile paralysis" has been a common disease for years, yet without paralysis no diagnosis has been positive. The early clinical picture is that of infection or meningitis; when properly coordinated it is only suggestive of poliomyelitis, and even with lumbar puncture there is still some degree of doubt. During the recent epidemic in Los Angeles I made a few hundred observations of a symptom in sixteen cases which seemed absolutely characteristic of the preparalytic stage. The symptom has been of great value to me, and inasmuch as it is not mentioned in any text-book or the recent literature I am submitting it to the readers ofThe Journalfor their criticism. <h3>NEW SYMPTOM</h3> The symptom referred to is a peculiar twitching, tremulous or convulsive movement of certain groups of muscles lasting from a few seconds to less than a minute. The amplitude of vibration is greater than a tremor, not
734-6 ANGUS: A New Approach to Three-dimensional Reconstruction of Geometry and Orientation of Coronary Lumen and Plaque by Combined Use of Coronary Angiography and IVUS
Authors: Camelis J. Slager, Martin Laban, Clemens von Birgelen, Rob Krams, Jan A.F. Oomen, Ad den Boer, Li Wenguang, Pim J. de Feyter, Patrick W. Serruys, Jos R.T.C. Roelandt
Journal: Journal of the American College of Cardiology (1995)
Hypersensitivity to Generic Drugs with Soybean Oil
Authors: Antonio Dueñas-Laita, Fernando Pineda, Alicia Armentia
Journal: New England Journal of Medicine (2009)

The authors reply: The analysis of CT colonography that Cash cites used a model that was validated in younger adult populations, 1 and the CMS's final decision memo noted that this model had been neither well tested nor previously used. 2 Furthermore, the memo acknowledged that this analysis combined outcomes from screening for colorectal cancer and abdominal aortic aneurysm.The Preventive Services Task Force recommends performing such screening only once in men who are 65 to 75 years of age and who have a history of smoking; the task force does not recommend such screening in women. 3Thus, less than one sixth of Medicare beneficiaries would be expected to have any benefit.Although the CMS reviewed other data showing that CT colonography is costeffective only at reimbursement levels that are much lower than current rates, 4 its decision was based primarily on the inadequacy of the evidence of benefit for this test and not its cost-effectiveness. 2 The CMS covers what is "reasonable and necessary." 5It would be irresponsible to cover services for which there are no clinical data show-ing benefits among its beneficiaries, since such services may be associated with harm -from additional unnecessary testing and procedures, anxiety about "incidentalomas," and additional diagnoses of uncertain clinical implications.It is essential that the CMS make decisions on the basis of high-quality clinical trials that reflect the effects on its elderly population.
Future perspectives and potential implications of cardiac myocyte apoptosis
Authors: A Haunstetter
Journal: Cardiovascular Research (2000)

Recent advances in the understanding of the molecular mechanisms of apoptosis has gained increasing interest in the cardiovascular research community. Apoptotic myocyte loss has been detected in different cardiac disease states such as ischemic heart disease and congestive heart failure. In addition, some evidence for the molecular mechanisms in cardiac myocyte apoptosis has been evolving, although at present the implications thereof for clinical cardiac disease are not known in most of the cases. Based on these new insights, it is the intention of this article to highlight some topics in apoptosis research that might be of particular interest to define the future role and potentials of new therapeutic approaches aimed at preventing myocyte apoptosis.
Abstract 2509: CDDO-Im induces DNA damage, G2/M arrest and apoptosis in BRCA1-mutated breast cancer cells
Authors: Eun-Hee Kim, Michael B. Sporn, Karen T. Liby
Journal: Cancer Research (2010)

Abstract The breast cancer-associated gene 1 (BRCA1) is the most frequently mutated tumor suppressor gene in familial breast cancers. BRCA1 mutations also predispose to other types of cancers, pointing to a fundamental role of this pathway in tumor suppression. BRCA1 plays important roles in DNA damage and repair, homologous recombination, cell-cycle regulation, and apoptosis. The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1, 9(11)-dien-28-oyl]imidazole (CDDO-Im) is a promising anticancer agent with potent anti-proliferative and apoptotic activities against a wide variety of cancer types. However the mechanisms responsible for the selective apoptotic effects of CDDO-Im in cancer cells remain elusive. In the present work, treatment of BRCA1-mutated mammary tumor cells with CCDO-Im (0.3-1 μM) led to apoptosis as characterized by decreased thymidine incorporation, increased annexin V-binding, and cleavage of PARP and caspases-3. In addition, 0.3 μM CDDO-Im treatment depleted the G1 population of cells, which was accompanied by an accumulation of cells at G2 phase. CDDO-Im also activated the DNA damage response by inducing the phosphorylation of Chk1/2 and the up-regulation of p21, prior to the induction of apoptosis in BRCA1-mutated cancer cells. The inhibition of Chk1 by UCN-01, a Chk1 inhibitor abrogated G2/M arrest induced by CDDO-Im. To investigate how CDDO-Im activates the DNA damage response in BRCA1-mutated breast cancer cells, we performed a comet assay and Western Blot for γH2AX, a marker of DNA damage. CDDO-Im induced DNA damage and the phosphorylation of H2AX in BRCA1-mutated mammary tumor cells. Pretreatment with 0.3 μM CDDO-Im sensitized BRCA1-mutated cancer cells to carboplatin, a DNA-damaging agent, suggesting that CDDO-Im potentiates the effect of this drug. Moreover, CDDO-Im also induced reactive oxygen species (ROS) generation in these tumor cells, which is associated with the induction of DNA damage. The inhibition of ROS generation by uric acid prevented CDDO-Im-induced DNA damage. Furthermore, treatment with CDDO-Im was not cytotoxic to normal mouse 3T3 fibroblasts, highlighting a selective therapeutic potential of CDDO-Im for BRCA1-associated breast cancer. Taken together, our results demonstrate that CDDO-Im induces ROS and subsequent DNA damage, thereby facilitating the activation of the DNA damage checkpoint, G2/M arrest and finally apoptosis in Brca1-mutated cancer cells. These findings are being explored in vivo to determine whether CDDO-Im could be used therapeutically for BRCA1-associated breast cancer. This study was supported by Breast Cancer Research Foundation. 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 2509.