tbuckley/cabot-search huggingface dataset:
THE EFFECT OF NOR-EPINEPHRINE ON THE ELECTROLYTE COMPOSITION OF ARTERIAL SMOOTH MUSCLE 1
Authors: Louis Tobian, Adacie Fox
Journal: Journal of Clinical Investigation (1956)

The changes in the electrolyte composition of ar- terial wall in renal and desoxycorticosterone in- duced hypertension (1) have stimulated us to in- vestigate the changes in the electrolytes of arterial smooth muscle that occur when an artery is brought under the influence of nor-epinephrine.The effects of this particular substance are es- pecially important since present evidence indicates that it is the main sympathetic neurohumoral agent affecting the peripheral arterial system.This study was first attempted with arterial rings in vitro using the Krebs-Henseleit medium.In this medium the control arteries lost large amounts of potassium, a situation which prompted an in vivo approach. METHODSAll dogs were given a standard dose of Nembutal® for anesthesia.The carotid was cannulated in each dog to provide a continuous recording of arterial blood pres- sure.In 12 dogs, the right femoral artery was ligated and quickly excised, stripped of adventitia, blotted free of blood, and placed in a polyethylene weighing bottle for
Heparan sulfate proteoglycan expression in chronic cholestatic human liver diseases
Authors: T Roskams
Journal: Hepatology (1996)

The mechanism of bile ductular reaction and accompanying fibrogenesis depends on interactions of ductular cells with the matrix and growth factors. Heparan sulfate proteoglycans (HSPGs) are essential cofactors in cell-matrix adhesion processes, in cell-cell recognition systems, and in receptor-growth factor interactions. We used monoclonal antibodies specific for the cell surface HSPGs (syndecans, glypican), for matrix HSPG (perlecan), and for heparan sulfate carbohydrate (HS) to investigate their immunohistochemical expression in 20 specimens with chronic cholestatic liver disease and in five normal human liver specimens. Because activated hepatic stellate cells (HSC are a major source of fibrosis in the liver, we also examined HSPG expression in primary cultures of human activated HSC using immunocytochemistry and Western blotting and for syndecan-1 also Northern blotting. In comparison with bile ductular cells of normal liver, reactive ductules in chronic cholestasis were marked by an elevated expression of syndecan-1, surrounded by an increased perlecan expression. In acinar zone 1, large stimulated macrophages and HSC, present in increased numbers, were strongly positive for syndecan-3. Cultured HSC showed a membranous staining pattern for syndecan-1, syndecan-3, and heparan sulfate, and in addition intracellular staining for syndecan-2, -3, and 4. Perlecan immunoreactivity was detected as intercellular strings. Western blotting revealed positive bands with all antibodies and Northern blotting for syndecan-1 was also positive. These results show that cultured human HSC can synthesize all four syndecans, glypican, and perlecan. These data reveal changes in the expression of syndecan-1, syndecan-3, and perlecan in human chronic cholestatic liver disease, that may be important in the deposition of matrix components and activation of growth factors that support ductular reaction and accompanying fibrogenesis.
Dose-dependent association of smoking and bronchial hyperresponsiveness
Authors: Maria Juusela, Paula Pallasaho, Eva Rönmark, Seppo Sarna, Anssi Sovijärvi, Bo Lundbäck
Journal: European Respiratory Journal (2013)

Our aim was to study the association of smoking habits and environmental tobacco smoke (ETS) exposure with bronchial hyperresponsiveness (BHR). A random sample of 292 adults was examined using a structured interview, spirometry, skin prick tests, exhaled nitric oxide fraction (FeNO) and bronchial histamine challenge. A large majority of subjects with BHR were smokers or ex-smokers. Starting to smoke before 20 years of age was significantly associated with BHR, as was current smoking, quantity of smoking and ETS exposure. The severity of BHR increased significantly with increasing pack-years of exposure (p<0.001). Current smokers with decreased lung function were at a particularly high risk of BHR. Impaired forced expiratory volume in 1 s and mean maximal expiratory flow were independent determinants for more severe BHR, regardless of age. In multivariate analysis, smoking remained an independent determinant for BHR after adjustment for impaired lung function and other covariates: ≥15 pack-years yielded an odds ratio of 3.00 (95% CI 1.33-6.76) for BHR. The association between BHR and FeNO was dependent on smoking habits. The results indicate that smoking is a significant risk factor for BHR, with a dose-dependent pattern, and that the severity of BHR increases with pack-years. The findings strongly suggest assessment of smoking habits in subjects with BHR.
Vaginal Spermicides and Congenital Disorders: The Validity of a Study-Reply
Authors: Lewis B. Holmes
Journal: JAMA (1986)

<h3>In Reply.—</h3> The article written by Drs Jick, Walker, Rothman, Watkins, and me (and several other individuals) has been the subject of a considerable amount of debate since its publication. Unfortunately, the article is often cited as showing a positive association between conception while using a spermicidal jelly and the occurrence of birth defects. Those citing the article in this way do not note the reservations expressed in the article about the findings, including the lack of information as to the mechanism by which nonoxynol 9 would reach the developing embryo, "the absence of a single, well-defined syndrome among the infants," the lack of information about the precise time of exposures, and the possibility of other confounding factors. The last sentence in the article notes our concerns about unanswered questions and the tentative nature of the findings. No articles published subsequently have shown unequivocal evidence that spermicides are teratogenic. In
bcl-6 in Lymphoma -- Sorting Out a Wastebasket?
Authors: Philip M. Kluin
Journal: New England Journal of Medicine (1994)

Non-Hodgkin's lymphomas are a heterogeneous group of disorders. Approximately 85 percent of them originate from B lymphocytes, and these B-cell lymphomas fall into the following main groups: lymphocytic lymphoma, follicular-center-cell lymphoma, mantle-cell lymphoma, diffuse large-cell lymphoma, and Burkitt's lymphoma. The mucosa-associated lymphoid-tissue (MALT) lymphomas, which occur in mucosal sites such as the stomach, form a separate category and may have a large-cell morphology. Of these various types, about 40 percent are diffuse large-cell lymphomas. In addition to distinctive cell-surface markers, there are characteristic genetic abnormalities in some kinds of lymphoma (Figure 1). These genetic disturbances often follow breakage of chromosomes . . .
Immunotherapeutic Potential of B7-DC (PD-L2) Cross-Linking Antibody In Conferring Antitumor Immunity
Authors: Suresh Radhakrishnan, Loc Tan Nguyen, Bogoljub Ciric, Dallas Flies, Virginia P. Van Keulen, Koji Tamada, Lieping Chen, Moses Rodriguez, Larry R. Pease
Journal: Cancer Research (2004)

A naturally occurring human antibody potentiates dendritic cell function on cross-linking B7-DC (PD-L2), supporting robust T-cell responses in vitro. Moreover, treatment of dendritic cells with B7-DC cross-linking antibody resulted in secretion of interleukin-12, suggesting a TH1 polarization of this response. Here we show an in vivo immunotherapeutic effect of this B7-DC cross-linking antibody using a poorly immunogenic B16 melanoma tumor model. Treatment of mice systemically with antibody at the time of tumor cell engraftment prevented tumor growth in a CD4 and CD8 T-cell-dependent manner. The protective effect of B7-DC cross-linking antibody treatment was independent of endogenous antibody responses. Tumor-specific CTL precursors could be isolated from lymph nodes draining the tumor site in animals treated with B7-DC cross-linking antibody, but not from those treated with isotype control antibodies. The elicited antitumor responses in vivo were specific and long-lasting. More strikingly, treatment of mice with B7-DC cross-linking antibody after the tumors were established in the lungs resulted in protection in a CD8-, perforin-, and granzyme B-dependent fashion. Depletion of natural killer cells did not block the effects of treatment with B7-DC cross-linking antibody. Together, these findings demonstrate that cross-linking B7-DC with the human IgM antibody sHIgM12 can induce a protective immune response against a weakly antigenic experimental tumor and therefore has potential as a novel immunotherapeutic approach for treating cancer.
Autoradiographic study of the 133Xenon disappearance method for measurement of myocardial blood flow
Authors: D. J. SHAW, A. PITT, G. C. FRIESINGER
Journal: Cardiovascular Research (1972)

Myocardial blood flow studied in canine hearts by the 133Xe disappearance method was better estimated by utilizing the initial portion of the disappearance curve than by 'curve-peeling'. Macroautoradiography demonstrated that radioactivity was located primarily in myocardium during the early portion of the curve, but in epicardial fat later. The method is incapable of detecting areas of reduced flow which can be demonstrated autoradiographically.
Renal Function Changes Following Surgery for Vascular Hypertension
Authors: Charles Heider
Journal: JAMA (1963)

INCREASED systemic blood pressure due to occlusive renal arterial disease is a potentially reversible form of diastolic hypertension. The offending anatomic lesion usually consists of narrowing or occlusion of the renal artery or its primary branches by atheromatous plaques, but it may be of other origin, either congenital or acquired.<sup>1</sup>The surgical goal in such cases is to preserve functional kidney tissue, whenever possible, with arterial revascularization by endarterectomy, angioplasty, or bypass graft.<sup>2-7</sup>Nephrectomy is performed only when these latter procedures are not technically feasible or when the involved kidney is nonfunctional. Although renovascular surgery or nephrectomy may result in blood pressure reduction, little information is available regarding renal functional changes in such cases following surgery. In the patients reported herein, long-term observations indicated that significant sustained blood pressure reduction was accomplished in 12 of 15 subjects treated by renal artery bypass or nephrectomy. It is the
Absence of Uterus.
Authors: H. W. Carpenter
Journal: JAMA (1891)

<h3>To the Editor:</h3> —The interesting case reported in No. 8 ofThe Journalby Dr. McShane, of Carmel, Ind., recalls to mind a case I had a few years since. A lady, aged 24 years, consulted me to ascertain why she could not have children. She had been married six years, was well developed, not masculine; breasts were normal, the pudendum normal, and well covered with hair. I found by digital examination a good-sized vagina, but no cervix uteri; in fact, there was nothing but a smooth, well arched vagina, about 4 inches in depth. I introduced a sound into the bladder, and with my finger in the rectum I could readily feel the sound, showing that there was complete absence of the uterus. Having been a member of the Association for several years, I think it best to let well enough alone and publishThe Journalat Chicago. Oneida,
The antimicrobial peptide rCRAMP is strongly upregulated during experimental arthritis in the rat
Authors: Markus H Hoffmann, Martin Herrmann, Birgitta Agerberth, Rikard Holmdahl
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Rheumatoid arthritis (RA) is characterised by an inflammatory and destructive infiltration of various immune cells into the synovium of the joint. The first cells to arrive at the site of inflammation and the main cell type in synovial fluid are neutrophil granulocytes that locally release cytotoxic agents, antimicrobial peptides, proteases and other inflammatory mediators, thus fuelling inflammation and damaging tissue. The aim of this project is to elucidate if locally released antimicrobial peptides contribute to the pathogenic events of arthritis. <h3>Materials and Methods</h3> Expression of the rat cathelicidin related antimicrobial peptide (rCRAMP) during the course of pristane-induced arthritis (PIA) in Dark Agouti rats was determined in blood, synovial blood, joint extracts, lymph nodes, spleens and livers by Western blotting, immunohistochemistry and fluorescence-activated cell sorting. Formation of neutrophil extracellular traps was analysed by 49-6-diamidino-2-phenylindole staining. IFN α was determined in sera by ELISA. Autoantibodies to rCRAMP were detected by immunoblot. <h3>Results</h3> In PIA, an animal model of arthritis that closely mimics RA, rCRAMP is strongly upregulated in the joints of arthritic animals. Interestingly, the strongest overexpression is seen around onset of clinical arthritis. rCRAMP expression is also upregulated in the blood of pristane-injected rats even before the onset of clinical arthritis. Upregulation after pristane injection can as well be seen in spleen, but not in pristane-draining lymph nodes or the liver. rCRAMP is mainly expressed in His48+ CD62L- granulocytes and a smaller fraction of monocytes. Pristane application induces NETs and causes accumulation of low density neutrophils that copurify with peripheral blood mononuclear cell. The increased expression of rCRAMP coincides with IgG and IgM autoantibodies to rCRAMP and elevated serum levels of type I Interferons in PIA rats. <h3>Conclusion</h3> Our results show strong upregulation of rCRAMP coinciding with pathological events in PIA. This might be due to a connection between rCRAMP forming complexes with nucleic acids that are locally released from damaged cells and activation of interferon-producing cells.
CD44 Attenuates Metastatic Invasion during Breast Cancer Progression
Authors: Jose I. Lopez, Todd D. Camenisch, Mark V. Stevens, Barbara J. Sands, John McDonald, Joyce A. Schroeder
Journal: Cancer Research (2005)

Abstract Metastatic invasion is the primary cause of breast cancer mortality, and adhesion receptors, such as CD44, are believed to be critical in this process. Historically, primary breast tumor epithelium has been investigated in isolation from other tissue components, leading to the common interpretation that CD44 and its primary ligand, hyaluronan, promote invasion. Here, we provide in vivo evidence showing CD44 antagonism to breast cancer metastasis. In a mouse model of spontaneously metastasizing breast cancer (MMTV-PyV mT), we found that loss of CD44 promotes metastasis to the lung. Localization studies, in combination with a novel hyaluronan synthase-GFP transgenic mouse, show a restricted pattern of expression for CD44 and hyaluronan. Whereas CD44 is expressed in tumor epithelium, hyaluronan synthase expression is restricted to stromal-associated cells. This distinct CD44 and hyaluronan pattern of distribution suggests a role for epithelial-stromal interaction in CD44 function. To define the relevance of this spatial regulation, we developed an in vitro invasion assay to emulate invasion into the extracellular matrix. Invasion of CD44-positive tumor cells was inhibited in hyaluronan-containing matrices, whereas blocking CD44-hyaluronan association increased invasion. Collectively, these data show that during breast cancer progression, hyaluronan-CD44 dynamics occurring through epithelial-stromal interactions are protective against metastasis.
Surgeons have insufficient experience to operate on children, report warns
Authors: A. Cole
Journal: BMJ (2009)

Some local paediatric services may be forced to close if surgeons who operate on children cannot get the necessary experience to maintain their skills, the Royal College of Surgeons has warned.

Its warning follows a critical report from the Healthcare Commission revealing that most surgeons in England and Wales who operate on children in common specialties are failing to carry out the recommended minimum level of 100 procedures involving children a year. In addition, most anaesthetists are falling short of the recommended 20 consultations with children each year.

A spokesperson for the Royal College of Surgeons said that there were strong arguments for treating non-specialist surgical operations such as …
Epstein-Barr virus persistence in the absence of conventional memory B cells: IgM+IgD+CD27+ B cells harbor the virus in X-linked lymphoproliferative disease patients
Authors: Sridhar Chaganti, Cindy S. Ma, Andrew I. Bell, Debbie Croom-Carter, Andrew D. Hislop, Stuart G. Tangye, Alan B. Rickinson
Journal: Blood (2008)
The Parkinson's disease–linked proteins Fbxo7 and Parkin interact to mediate mitophagy
Authors: Victoria S Burchell, David E Nelson, Alvaro Sanchez-Martinez, Marta Delgado-Camprubi, Rachael M Ivatt, Joe H Pogson, Suzanne J Randle, Selina Wray, Patrick A Lewis, Henry Houlden, Andrey Y Abramov, John Hardy, Nicholas W Wood, Alexander J Whitworth, Heike Laman, Helene Plun-Favreau
Journal: Nature Neuroscience (2013)
Say no to the free lunch
Authors: Fiona Godlee
Journal: BMJ (2005)

like determining if the efficacy observed in randomised controlled trials translates into effectiveness in broader populations and more realistic settings, and to provide information on adverse events and risks.In the first of three articles on critical appraisal of cohort studies, Gurwitz and colleagues (p 895) explain the role of cohort studies in the hierarchy of evidence, the characteristics of their design, and how selection bias can compromise their validity.
The Involuting Hemangioma
Authors: Frederick A. J. Kingery
Journal: JAMA (1965)

The involuting hemangioma, or strawberry birthmark, is small or absent at the time of birth. During the first six or eight months of life it increases rapidly in size, and then gradually regresses over the next one to five years. In the uncomplicated lesion the best eventual result is achieved with no treatment at all. Observation alone is not possible, however, when the tumor is so situated that it interferes with the visual axis, or disturbs such vital functions as breathing or sucking. Active treatment in the form of ionizing radiation, cryotherapy, or surgical removal is sometimes necessary to preserve these functions. The tumor should not be confused with a cavernous hemangioma, which is present at birth and grows slowly as the child grows. Composed of mature endothelial cells, the cavernous hemangioma is radiation resistant, unaffected by cryotherapy, and shows no tendency toward spontaneous involution. Difficulty arises when the parents
Contempo '81. Oncology
Authors: E. M. McKelvey
Journal: JAMA (1981)

The dramatic therapeutic responses that have been achieved in patients with leukemia, lymphoma, and certain other tumors have led to increased anticipation for the treatment of all patients with malignant disease. While major developments have occurred in different areas of clinical oncology, this past year has been characterized as one of direct clinical application of advances in basic science and technology. In addition, the lessons learned from the treatment of one type of cancer have been incorporated into the management of other forms of malignant neoplasms. <h3>Cancer Detection</h3> The ability to diagnose, stage, and monitor malignant disease accurately is an essential part of the care of patients with cancer. Recent progress in this area has been made with the use of radiolabeled antibodies to specific tumor markers. Historically, the detection and serological quantitation of selected tumor-markers have proved to be of limited clinical value because of lack of specificity and
Some Remarks on the Influenza Bacillus
Authors: E. Klein
Journal: BMJ (1892)

Ill rural districts, as we have seen, it is possible that influenza may be recognised as a "dangerous infectious dis- ease," and then the sanitary authorities may and ought to fine patients who expose themselves whilst suffering from-it.No such provision giving such power exists in the London Act.At the present time anyone may without let or hind- rance, whilst suffering from influenza, go to any public place, drive in any public conveyancb, and spread a disease which, as we have seen, was in the year 1890 responsible for the death of over 27,000 people.Now, Mr. President, this does not seem to be an ideal hygienic arrangement.It is worthy of note that there is at
A comparison of high-dose (HD, 500 mg) fulvestrant vs anastrozole (1 mg) as first-line treatments for advanced breast cancer: results from FIRST.
Authors: MJ Ellis, A Llombart, J Rolski, D Feltl, E Macpherson, J Lindemann, JF Robertson
Journal: Cancer Research (2009)

Abstract Abstract #6126 Background: The estrogen-receptor (ER) antagonist fulvestrant (Faslodex™) at the approved dose (AD, 250mg) has confirmed efficacy in postmenopausal women with advanced breast cancer following recurrence or progression on an anti-estrogen. However, evidence suggests that higher doses may have greater biological and clinical activity. A recent neoadjuvant study in patients with ER+, locally advanced disease showed significantly greater reductions in Ki67 LI and ER expression for fulvestrant high dose (HD, 500 mg) compared with AD.&amp;#x2028; Methods: FIRST (Fulvestrant fIRst-line Study comparing endocrine Treatments) is a Phase II, randomized, open-label, multicentre study comparing fulvestrant HD (500 mg/month [2×250 mg im injections] plus 500 mg on Day 14 of Month 1) vs anastrozole (1 mg/day) as first-line treatments for postmenopausal women with advanced breast cancer. Eligible patients had no prior treatment for advanced disease and ER+, evaluable disease. Patients received treatment until disease progression or an event necessitating discontinuation. The primary endpoint was clinical benefit rate (CBR), ie the proportion of patients achieving a complete response, a partial response or stable disease for ≥24 weeks. Secondary endpoints included: objective response (OR), time to progression (TTP), duration of response (DoR), duration of clinical benefit (DoCB) and tolerability (adverse events [AEs] and laboratory tests).&amp;#x2028; Results: In total, 205 women (median age 67 years) were included (fulvestrant HD: n=102; anastrozole: n=103). Median follow-up was 6.5 months. CBR was similar between treatments: fulvestrant HD 72.5%, anastrozole 67.0% (odds ratio 1.3023, 95% confidence interval [CI] 0.7170, 2.3976, p=0.3860). OR rates were: fulvestrant HD 36%, anastrozole 35.5%. Median TTP for anastrozole: 12.5 months; fulvestrant HD: not yet reached, corresponding to a 60% longer TTP for fulvestrant HD (hazard ratio=0.6266, 95% CI 0.3929, 0.9991, p=0.0496). DoR and DoCB were also numerically longer for fulvestrant HD. Both treatments were well tolerated, with no significant differences in the incidence of pre-specified AEs or the small number of withdrawals due to AEs.&amp;#x2028; Discussion: Fulvestrant HD offers CB and OR rates similar to those obtained with anastrozole 1 mg, with a significantly longer TTP. Fulvestrant HD was well tolerated, with no unexpected AEs. The AE profile of fulvestrant HD appears consistent with the known toxicity profile of the AD. These results are encouraging and provide further support for the improved clinical activity anticipated with fulvestrant HD. Confirmation of these findings is awaited from an ongoing Phase III, double-blind comparison of fulvestrant HD and AD (CONFIRM). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6126.
A Matter of Clarity
Authors: H. L. Puckett
Journal: JAMA (1963)

<h3>To the Editor:—</h3> In reference to Fracture of the Month 33 (<i>JAMA</i><b>183</b>:1099 [March 30] 1963) why confuse the medical profession and the medical students now and hereafter with the term "osteopenia"? It seems to me that the term "osteoporosis" was good enough for Albright and Reifenstein, and it should be descriptive enough for the rest of the profession until we learn more about the disease than we know now.