tbuckley/cabot-search huggingface dataset:
An Editorial Viewpoint
Authors: Carl C. Seltzer
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Drill and Calhoun claim a lack of association between the administration of oral contraceptives and the occurrence of thromboembolic disease. The critical reply to this article by Doll, Inman, and Vessey serves to highlight the opposing views of the English studies. The fundamental differences in study designs employed in the English and American investigation may account for the different results obtained. The English study is a matched case/control study. It is based on the comparison of oral contraceptive usage in young married women hospital patients with thromboembolic disease with that of a nonthromboembolic control series from the same hospitals, carefully matched for age, parity, date of admission, and absence of any predisposing cause for thromboembolic disease. The reliability of the data appears to be high with respect to disease diagnosis, and the affected sample was representative of a substantial segment of the English population. In contrast, the
Effect of acute and chronic acidaemia and associated hypoxia on the pulmonary circulation of patients with chronic bronchitis
Authors: E. Housley, S. W. Clarke, R. B. Hedworth-Whitty, J. M. Bishop
Journal: Cardiovascular Research (1970)

It has been suggested that the increased hydrogen ion concentration in chronic bronchitis is a significant factor in the pulmonary hypertension of this condition. In this study acute increases in hydrogen ion concentration with HCl infusion, and chronic increases with oral ammonium chloride, did not cause pulmonary vasoconstriction in patients with bronchitis and thus did not support this hypothesis.
Pathologic Blood Flow in Pulmonary Vascular Disease as Shown by Gated Magnetic Resonance Imaging
Authors: GUSTAV K. von SCHULTHESS
Journal: Annals of Internal Medicine (1985)

Axial, dual spin-echo magnetic resonance (MR) images, taken at the level of the pulmonary arteries and gated to the cardiac cycle, were qualitatively and quantitatively evaluated in nine patients with primary pulmonary arterial hypertension and six controls. In controls and patients, intravascular signal intensity was higher during diastole than during systole when fast flow conditions exist in the arteries; however, patients with severe pulmonary arterial hypertension showed significantly higher signals in the pulmonary arteries than did controls. A correlation between pulmonary vascular resistance and the MR signal in the right pulmonary artery in early systole (r = 0.89) showed the ability of MR images to provide information on blood flow and suggests a role for magnetic resonance in assessing the severity of this disease noninvasively. Flow-related cardiosynchronous variations in the lung parenchyma of controls were also observed; with further development, magnetic resonance may become useful to measure tissue perfusion and provide both pathoanatomic and pathophysiologic information. Furthermore, there was a significant difference between the MR signal intensity of dorsal and ventral lung regions.
Continuous Intravascular Secretion of Endostatin in Mice from Transduced Hematopoietic Stem Cells
Authors: Robert Pawliuk, Thomas Bachelot, Omar Zurkiya, Anna Eriksson, Yihai Cao, Philippe Leboulch
Journal: Molecular Therapy (2002)

Endostatin, a 20-kDa carboxy-terminal fragment of collagen XVIII, is the leading member of a class of physiologic inhibitors of angiogenesis with potent antitumor activity. Repeated subcutaneous administration of recombinant endostatin in mice led to permanent regression of established tumors to a microscopic dormant state and prompted the initiation of human clinical trials. However, a discrepancy remained unresolved: sustained tumor regression has only been observed with a non-soluble, precipitated form of recombinant endostatin produced in bacteria. To shed light on this question and establish a model of systemic anti-angiogenic gene therapy of cancer that may surmount obstacles in protein production and delivery, we transduced murine hematopoietic stem cells with a retrovirus encoding a secretable form of endostatin. Despite continuous, high-level secretion of endostatin in the vasculature of all transplanted mice, we detected neither inhibition of in vivo neoangiogenesis nor antitumor activity. Resolution of this paradox may come from human trials of endostatin now underway.
A Stress-Induced, Superoxide-Mediated Caspase-1 Activation Pathway Causes Plasma IL-18 Upregulation
Authors: Atsuo Sekiyama, Haruyasu Ueda, Shin-ichiro Kashiwamura, Ryuji Sekiyama, Masatoshi Takeda, Kazuhito Rokutan, Haruki Okamura
Journal: Immunity (2005)
Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial angiogenesis
Authors: Yun-Hee Bae, Hyun-Joo Park, Su-Ryun Kim, Jee-Young Kim, Youra Kang, Jung-Ae Kim, Hee-Jun Wee, Ryoichiro Kageyama, Jin Sup Jung, Moon-Kyoung Bae, Soo-Kyung Bae
Journal: Cardiovascular Research (2010)

AimsOur aims were to determine the role of Notch1 in mediating visfatin-induced angiogenesis and to explore potential target genes involved.
Towards the safer use of medicines
Authors: A W Asscher, G D Parr, V B Whitmarsh
Journal: BMJ (1995)

In Britain the tools are now available to provide better information on safety of medicines in both hospital and community settings, and this could be done at relatively modest cost. The needs of patients, doctors, and pharmacists are changing; although more research is needed, such information as is presently available must be both better and more widely publicised and understood. Universities, government, the pharmaceutical industry, and educated journalism all have an important part to play in this process.
Interleukin‐33 requires <scp>CMRF</scp>35‐like molecule‐1 expression for induction of myeloid cell activation
Authors: D. Shik, I. Moshkovits, D. Karo‐Atar, H. Reichman, A. Munitz
Journal: Allergy (2014)

Abstract Background IL ‐33 is a potent activator of various cells involved in allergic inflammation, including eosinophils and mast cells. Despite its critical role in Th2 disease settings, endogenous molecular mechanisms that may regulate IL ‐33‐induced responses remain to be defined. We have recently shown that eosinophils express CMRF 35‐like molecule ( CLM )‐1. Yet, the role of CLM ‐1 in regulating eosinophil functions is still elusive. Methods CLM‐1 and CLM ‐8 expression and cellular localization were assessed in murine bone marrow‐derived and/or peritoneal cells at baseline and following IL ‐33 stimulation (flow cytometry, western blot). IL ‐33‐induced mediator release and signaling were assessed in wild‐type (wt) and Clm1 −/− cells and mice. Results BM ‐derived eosinophils express high levels of glycosylated CLM ‐1. IL ‐33 induced a rapid, specific, concentration‐ and time‐dependent upregulation of CLM ‐1 in eosinophils ( in vitro and in vivo ) . Clm1 −/− eosinophils secreted less IL ‐33‐induced mediators than wt eosinophils. CLM ‐1 co‐localized to ST 2 following IL ‐33 stimulation and was required for IL ‐33‐induced NF κB and p38 phosphorylation. Th2 cytokine (e.g., IL ‐5, IL ‐13) and chemokine (e.g., eotaxins, CCL 2) secretion was markedly attenuated in IL ‐33‐treated Clm1 −/− mice. Subsequently, IL ‐33‐challenged mice displayed reduced infiltration of mast cells, macrophages, neutrophils, and B cells. Despite the markedly impaired IL ‐33‐induced eotaxin expression in Clm1 −/− mice, eosinophil accumulation was similar in wt and Clm1 −/− mice, due to hyperchemotactic responses of Clm1 −/− eosinophils. Conclusions CLM ‐1 is a novel regulator of IL ‐33‐induced eosinophil activation. These data contribute to the understanding of endogenous molecular mechanisms regulating IL ‐33‐induced responses and may ultimately lead to receptor‐based tools for future therapeutic intervention in IL ‐33‐associated diseases.
Recurrent Spontaneous Cervical-Artery Dissection
Authors: Wouter I. Schievink, Bahram Mokri, W. Michael O'Fallon
Journal: New England Journal of Medicine (1994)

Spontaneous dissection of the internal carotid and vertebral arteries is increasingly recognized as a cause of ischemic stroke in young people. An underlying arteriopathy is often suspected in the pathogenesis of such dissection, but the frequency of recurrent dissection is unknown.We describe the long-term follow-up of 200 consecutive patients (104 women and 96 men) with spontaneous cervical-artery dissections evaluated at the Mayo Clinic between 1970 and 1990. All diagnoses were confirmed by angiography.The mean age of the patients was 44.9 years (range, 16 to 76). Internal carotid arteries were affected in 150 patients, vertebral arteries in 37, and both in 13. Multivessel dissections were present in 28 percent of the patients. The mean follow-up was 7.4 years. Recurrent dissection occurred only in arteries not previously involved by dissection. A recurrent arterial dissection developed in 16 patients (8 percent)--within a month after the initial dissection in 4 patients (2 percent) and between 1.4 and 8.6 years later in 12 patients (a rate of 1 percent per year). The cumulative rate of recurrent dissection among patients followed for 10 years was 11.9 percent. Younger patients had a greater risk of recurrent dissection.Although dissections in multiple cervical vessels are common at presentation, after the first month the risk of recurrent dissection is only about 1 percent per year.
Abstract 2102: The germline nonsense variant K1019X results in loss of tumor suppressing function of EphB2 in prostate cancer cells
Authors: Bodour Salhia, Khateeb Hyder Hussain, John Carpten
Journal: Cancer Research (2011)

Abstract Prostate cancer (PC) is the most common form of cancer in all men and also the second leading cause of cancer related deaths. On average, African American (AA) males are twice as likely to develop prostate cancer and three times more likely to die from it compared with Caucasian men. Previously we combined nonsense-mediated RNA decay microarrays and array-based comparative genomic hybridization for the genome-wide identification of genes with biallelic inactivation involving nonsense mutations and loss of the wild-type allele (Huusko et al, Nature Genetics 2004). This approach enabled us to identify previously unknown mutations in the receptor tyrosine kinase gene EphB2 in ∼7% of prostate tumors. EPHB2 is a member of the tyrosine kinase receptor family of proteins and regulates intracellular signaling pathways involved in cell growth, migration, adhesion, and polarity. Furthermore, there is also strong evidence for EphB2 as a tumor suppressor in colorectal cancer. There are two main isoforms (1 and 2) of the EphB2 gene, which is the result of alternative splicing. Previous studies from our lab also shows that a germline 3055A&amp;gt;T nonsense variant (K1019X) in the EphB2 gene differs in frequency between AA and Caucasian males, is associated with increased risk for PC in AA men with a positive family history, and may be an important genetic risk factor for prostate cancer in AA. The DU145 prostate cancer cell line, originating from a brain metastasis, carries a truncating mutation of isoform 1 of EphB2 and a deletion of the remaining allele. Transfection of DU145 cells, which lack functional EPHB2, with wild-type EPHB2 suppresses clonogenic growth. The goal of this project is to determine the effect of the K1019X mutation on the growth of DU145 cells. Introduction of wild-type and 3055A&amp;gt;T EphB2 into DU145 cells using a lentiviral-based vector led to successful expression as seen by RT-PCR and western blot analysis. We also demonstrated using RT-PCR and western blot analysis that while DU145 cells lack functional expression of the isoform 1, there is expression of the second isoform, implying that the tumor suppressing function of EPHB2 may be unique to isoform 1. Using a sulforhodamine B assay we demonstrated that the K1019X mutation inhibits growth suppression of DU145 cells as compared with wild-type EPHB2. These initial findings suggest that the K1019X is a true functional variant and support the role of the K1019X in increasing prostate cancer risk in AA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2102. doi:10.1158/1538-7445.AM2011-2102
Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling
Authors: Gillian I Rice, Yoandris del Toro Duany, Emma M Jenkinson, Gabriella M A Forte, Beverley H Anderson, Giada Ariaudo, Brigitte Bader-Meunier, Eileen M Baildam, Roberta Battini, Michael W Beresford, Manuela Casarano, Mondher Chouchane, Rolando Cimaz, Abigail E Collins, Nuno J V Cordeiro, Russell C Dale, Joyce E Davidson, Liesbeth De Waele, Isabelle Desguerre, Laurence Faivre, Elisa Fazzi, Bertrand Isidor, Lieven Lagae, Andrew R Latchman, Pierre Lebon, Chumei Li, John H Livingston, Charles M Lourenço, Maria Margherita Mancardi, Alice Masurel-Paulet, Iain B McInnes, Manoj P Menezes, Cyril Mignot, James O'Sullivan, Simona Orcesi, Paolo P Picco, Enrica Riva, Robert A Robinson, Diana Rodriguez, Elisabetta Salvatici, Christiaan Scott, Marta Szybowska, John L Tolmie, Adeline Vanderver, Catherine Vanhulle, Jose Pedro Vieira, Kate Webb, Robyn N Whitney, Simon G Williams, Lynne A Wolfe, Sameer M Zuberi, Sun Hur, Yanick J Crow
Journal: Nature Genetics (2014)
Prognosis of Women With Primary Breast Cancer Diagnosed During Pregnancy
Authors: Diana Crivellari, Loredana Militello
Journal: Journal of Clinical Oncology (2013)

ClinicalOncology, Amant et al 1 reported the results from an international collaborative study on prognosis of women with primary breast cancer diagnosed during pregnancy.Their results contrast with those of a recent report 2 on a meta-analysis of 30 studies derived from the literature and that showed a significantly higher risk of death for patients diagnosed during pregnancy or 1 year afterward, with a particular risk for those diagnosed postpartum; this group of patients was not included in the Amant study.In addition, there was no statistically significant difference in disease-free and overall survival at a median follow-up of 61 months in the overall group of 311 evaluable patients.The majority of these patients had triple-negative or human epidermal growth factor receptor 2-positive disease (118 and 145 patients respectively, whereas there were 145 endocrine-responsive patients overall).For these patients at higher risk, no or little effect of hormonal milieu may be anticipated, and activity of targeted agents may have contributed to improve prognosis.On the other hand, in the luminal B cohort a hazard ratio (HR) of 1.73 in overall survival with an extremely large 95% CI (0.63 to 4.75) was reported in the 109 pregnant patients.In their discussion, the authors did not mention this fact.They simply concluded that they found similar survival for patients with pri-mary breast cancer diagnosed during pregnancy when compared with nonpregnant patients after adjusting for known prognostic factors.To better understand differences in the biology of breast cancer this may be at least in part true for triple-negative disease (HR, 1.04; 95% CI, 0.51 to 2.09) or human epidermal growth factor receptor 2-positive disease (HR, 1.34; 95% CI, 0.51 to 3.54) but may be not the case for endocrine-responsive breast cancer, given that only 46 patients were considered with luminal A and 99 patients with luminal B breast cancer (HR, 0.60; 95% CI, 0.08 to 4.68).Therefore, according to our opinion, the conclusions of the authors should be taken with caution particularly for endocrineresponsive patients.As we have no data from evidence-based studies, the issue of the recommendation to proceed with a pregnancy in young hormoneresponsive patients remains an open question.
PELVIC IRRADIATION IN THE CHILD-BEARING WOMAN
Authors: PALMER FINDLEY
Journal: JAMA (1930)

Irradiation therapy has encroached on the field of surgery to an ever increasing degree and is destined to make still greater inroads as the result of improved technic. It is fair to assume that there can be no epoch-making advances in the field of pelvic surgery. It remains to be seen how far pelvic lesions can be controlled and eradicated by means other than surgery. At the present time interest largely centers in the x-rays and radium as substitutes for surgery in the treatment of certain pelvic disorders. Gynecologists and radiologists are not wholly in accord on the management of pelvic lesions found after the child-bearing period, but the problem becomes enormously complicated in the earlier years of sex life. To control hemorrhage, to relieve intolerable pain of menstruation, to check the growth of fibroid tumors and to alleviate their symptoms without producing permanent amenorrhea and sterility are indeed vexing
Comparative trial of volunteer and professional treatments of dysphasia after stroke.
Authors: M Meikle, E Wechsler, A Tupper, M Benenson, J Butler, D Mulhall, G Stern
Journal: BMJ (1979)

A study of the treatment of dysphasia after stroke compared the progress of two groups of disabled patients. One received conventional treatment from qualified speech therapists and the other from non-professional volunteers. Methods of assessing communication difficulties were also compared and the impact of aphasic illness on families examined. No important differences in the results of treatment were seen between the two groups. The volunteers, however, often had to assume some of the responsibilities of social workers, and transport to hospital created practical and economic problems. It is concluded that the two forms of treatment provide essentially the same benefit, although doubt must still remain because relatively few patients were studied.
Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1
Authors: M. Resti, C. Azzari, F. Mannelli, M. Moriondo, E. Novembre, M. de Martino, A. Vierucci
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To determine the risk factors for and timing of vertical transmission of hepatitis C virus in women who are not infected with HIV-1. <b>Design:</b> Follow up for a median of 28 (range 24-38) months of babies born to women with antibodies to hepatitis C virus but not HIV-1. <b>Subjects:</b> 442 mothers and babies, of whom 403 completed the study. <b>Main outcome measures:</b> Presence of antibodies to hepatitis C virus and viral RNA and alanine aminotransferase activity in babies. Presence of viral RNA, method of infection with hepatitis C, method of delivery, and type of infant feeding in mothers. <b>Results:</b> 13 of the 403 children had acquired hepatitis C virus infection at the end of follow up. All these children were born to women positive for hepatitis C virus RNA; none of the 128 RNA negative mothers passed on the infection (difference 5%, 95% confidence interval 2% to 7%). 6 children had viral RNA immediately after birth. 111 women had used intravenous drugs and 20 had received blood transfusions. 11 of the infected children were born to these women compared with 2 to the 144 with no known risk factor (difference 7%, 2% to 12%). <b>Conclusions:</b> This study suggests that in women not infected with HIV only those with hepatitis C virus RNA are at risk of infecting their babies. Transmission does seem to occur in utero, and the rate of transmission is higher in women who have had blood transfusions or used intravenous drugs than in women with no known risk factor for infection. <h3>Key messages</h3> Little information exists on vertical transmission of hepatitis C virus in women not infected with HIV This study in a large unselected population of infants born to HIV-1 negative mothers suggests that intravenous drug use itself is an important risk factor for transmission of hepatitis C virus Maternal post-transfusional hepatitis is also an important risk factor for infection of infants Viral genotype, maternal viraemia, type of delivery (vaginal delivery or caesarean section) and breast feeding do not seem to be risk factors In utero transmission of hepatitis C virus has been suggested by RNA positivity on day of birth in some infected children
The Transfer of Alcohol to Human Milk
Authors: Julie A. Mennella, Gary K. Beauchamp
Journal: New England Journal of Medicine (1991)

The amount of alcohol ingested by a breast-fed infant is only a small fraction of that consumed by its mother, but even this small amount may have an effect on the infant. We investigated whether the ingestion of alcohol by a lactating woman altered the odor of her milk and whether exposure to a small amount of alcohol in the mother's milk had immediate effects on the behavior of the infant.
Book Review Diagnostic Atlas of the Heart Edited by J. Willis Hurst and Joseph S. Alpert, with Robert H. Anderson, Anton E. Becker, and Benson R. Wilcox. 560 pp., illustrated. New York, Raven Press, 1994. $150. 0-7817-0058-2
Authors: David H. Spodick
Journal: New England Journal of Medicine (1994)
Complications With Percutaneous Central Venous Catheters
Authors: Max B. Walters
Journal: JAMA (1972)

The incidence of complications following the insertion of central venous catheters in acute myocardial infarction was determined in 240 cases. All catheters were inserted percutaneously. Infection occurred rarely: one patient was successfully treated for<i>Staphylococcus aureus</i>septicemia and one for a local infection. Phlebitis occurred in 16% of cases. Only four patients had symptomatic subclavian vein thrombosis, yet routine phlebograms in 20 consecutive patients showed four instances of asymptomatic axillary vein thrombosis. Anticoagulant therapy was of no value in preventing thrombus formation.
The Blalock-Taussig-Thomas Collaboration
Authors: Anne M. Murphy
Journal: JAMA (2008)

Heretofore there has been no satisfactory treatment for pulmonary stenosis and pulmonary atresia. A “blue” baby with a malformed heart was considered beyond the reach of surgical aid. During the past three months we have operated on 3 children with severe degrees of pulmonary stenosis and each of the patients appears to be greatly benefited. In the second and third cases, in which there was deep persistent cyanosis, the cyanosis has greatly diminished or has disappeared and the general condition of the patients is proportionally improved. The results are sufficiently encouraging to warrant an early report.The operation here reported and the studies leading thereto were undertaken with the conviction that even though the structure of the heart was grossly abnormal, in many instances it might be possible to alter the course of the circulation in such a manner as to lessen the cyanosis and the resultant disability. It is important to emphasize the fact that it is not the cyanosis, per se, which does harm. Nevertheless, since cyanosis is a striking manifestation of the underlying anoxemia and the compensatory polycythemia, a brief discussion of the causes of cyanosis and the factors operative in congenital malformations of the heart is essential in order to understand the principles underlying the present operation.See PDF for full text of the original JAMA article.