tbuckley/cabot-search huggingface dataset:
Role and mechanisms of action of acetylcholine in the regulation of rat cholangiocyte secretory functions.
Authors: D Alvaro, G Alpini, A M Jezequel, C Bassotti, C Francia, F Fraioli, R Romeo, L Marucci, G Le Sage, S S Glaser, A Benedetti
Journal: Journal of Clinical Investigation (1997)

We investigated, in isolated bile duct units (IBDU) and cholangiocytes isolated from normal rat liver, the occurrence of acetylcholine (ACh) receptors, and the role and mechanisms of ACh in the regulation of the Cl-/HCO3- exchanger activity. The Cl-/HCO3- exchanger activity was evaluated measuring changes in intracellular pH induced by acute Cl- removal/readmission. M3 subtype ACh receptors were detected in IBDU and isolated cholangiocytes by immunofluorescence, immunoelectron microscopy, and reverse transcriptase PCR. M1 subtype ACh receptor mRNA was not detected by reverse transcriptase PCR and M2 subtype was negative by immunofluorescence. ACh (10 microM) showed no effect on the basal activity of the Cl-/HCO3- exchanger. When IBDU were exposed to ACh plus secretin, ACh significantly (P < 0.03) increased the maximal rate of alkalinization after Cl- removal and the maximal rate of recovery after Cl- readmission compared with secretin alone (50 nM), indicating that ACh potentiates the stimulatory effect of secretin on the Cl-/HCO3- exchanger activity. This effect of ACh was blocked by the M3 ACh receptor antagonist, 4-diphenyl-acetoxy-N-(2-chloroethyl)-piperidine (40 nM), by the intracellular Ca2+ chelator, 1,2-bis (2-Aminophenoxy)- ethane-N,N,N', N'-tetraacetic acid acetoxymethylester (50 microM), but not by the protein kinase C antagonist, staurosporine (0.1 microM). Intracellular cAMP levels, in isolated rat cholangiocytes, were unaffected by ACh alone, but were markedly higher after exposure to secretin plus ACh compared with secretin alone (P < 0.01). The ACh-induced potentiation of the secretin effect on both intracellular cAMP levels and the Cl-/HCO3- exchanger activity was individually abolished by two calcineurin inhibitors, FK-506 and cyclosporin A (100 nM). Conclusions: M3 ACh receptors are markedly and diffusively represented in rat cholangiocytes. ACh did not influence the basal activity of the Cl-/HCO3- exchanger, but enhanced the stimulation by secretin of this anion exchanger by a Ca2+-dependent, protein kinase C-insensitive pathway that potentiates the secretin stimulation of adenylyl cyclase. Calcineurin most likely mediates the cross-talk between the calcium and adenylyl cyclase pathways. Since secretin targets cholangiocytes during parasympathetic predominance, coordinated regulation of Cl-/HCO3- exchanger by secretin (cAMP) and ACh (Ca2+) could play a major role in the regulation of ductal bicarbonate excretion in bile just when the bicarbonate requirement in the intestine is maximal.
TCT-891 Outcomes Of Transcatheter Aortic Valve Replacement Versus Standard Therapy Among Women Deemed Too High Risk For Surgery In The PARTNER Trial
Authors: Susheel Kodali, Karin Humphries, Vuyisile Nkomo, Lars Svensson, Neil Weissman, David Cohen, Vinod Thourani, Michael Mack, E. Murat Tuzcu, Irene Hueter, Maria Alu, Ajay Kirtane, Martin Leon
Journal: Journal of the American College of Cardiology (2012)
Association of Extended Work Shifts, Vascular Function, and Inflammatory Markers in Internal Medicine Residents: A Randomized Crossover Trial
Authors: Haoyi Zheng, Milan Patel, Katarzyna Hryniewicz, Stuart D. Katz
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 230: LMP1 function in NK/T-cell lymphoma
Authors: Kim Nuri
Journal: Cancer Research (2010)

Abstract BACKGROUND: Because NK/T-cell lymphoma was closely associated with EBV LMP1 (latent membrane protein-1) which can directly activate NF-κB-mediated oncoproteins, therefore, in this study determined whether bortezomib (proteasome inhibitor) alone or combined with irradiation affect cytotoxicity and related mechanism in NK/T-cell lymphoma and malignant lymphoid cell lines. Beside, recently LMP1 has been introduced ambivalent function, because it's also up-regulation of Fas signaling. However, lack of information when these are activated by various stimulations. Therefore, in this study, we showed that bortezomib can enhance up-regulation of LMP1 as pro-apoptotic protein in EBV LMP1 expressed cell lines. MATERIAL &amp; METHOD: Human NK/T-cell lymphoma cells (Hank-1), NK-cell lymphoma (NK-92), T-cell lymphoma cells (Jurkat), and Burkitt lymphoma cells (Raji and Jijoye) were used. Bortezomib and irradiation were treated alone or combined, and tumor cell growth and apoptosis were measured by MTT assay and FACS respectively. Apoptosis and its associated protein expression levels were measured by Western blot assay. Interaction of LMP1 and Fas were evaluated by immuno-precipitation and protein ligation assay. RESULTS: Cell death by combining of bortezomib and irradiation synergistically inducing in LMP1 expressed Hank-1 than no LMP1 expressed NK-92 cells. To understand the mechanism of bortezomib regulated LMP1 and Fas, we examined that activated LMP1 by bortezomib enhanced effect of irradiation inducing cytotoxicity. Combined treatment of bortezomib and irradiation up-regulated LMP1 and Fas which composed binding complex, activating Fas-related molecules. In this regard, LMP1 may have paradoxal behavior. These results provided that combination of bortezomib and irradiation enhanced LMP1 as pro-apoptotic function, leading to degradation of NF-κB and resulted caspase activation in EBV LMP1 expressed cancer cell lines. CONCLUSION: LMP1 is able to inducing NF-κB in normal condition as oncoprotein, however bortezomib could up-regulate LMP1, its binding with Fas in EBV LMP1 expressed lymphoid cancer cell lines. Therefore, combination of bortezomib and irradiation is suggested as potential therapy not only in NK/T-cell lymphoma but also LMP1 expressed lymphoma and tumors. 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 230.
Prognosis of 1000 young women studied by coronary angiography.
Authors: W L Proudfit, C C Welch, C Siqueira, F P Morcerf, W C Sheldon
Journal: Circulation (1981)

One thousand women younger than age 50 years suspected of having coronary disease were followed for at least 5 years (average 8.4 years) to determine their course after coronary arteriography. Three patients were lost to follow-up; all had normal arteriograms. The survival rate was 96.9% at 5 years for 761 patients who had less than 50% narrowing of any artery. One patient who had coronary ectasia died within 5 years, and one woman who had minimal lesions suffered sudden death. Seven of 727 women who had normal arteries or less than 30% narrowing of any artery had coronary events (death, myocardial infarction, bypass operation for progressive disease), and six of 34 women who had 30 to almost 50% obstruction of at least one artery had coronary events. Calculations of survival for 236 women who had severe coronary lesions were affected by withdrawal for operation. Five-year survival was 74%.
Correlates of one-year survival inpatients with cardiogenic shock complicating acute myocardial infarction
Authors: Timothy A. Sanborn, Lynn A. Sleeper, John G. Webb, John K. French, Geoffrey Bergman, Manish Parikh, S.Chiu Wong, Jean Boland, Matthias Pfisterer, James N. Slater, Samin Sharma, Judith S. Hochman
Journal: Journal of the American College of Cardiology (2003)
Clinical Potential of Intravascular Ultrasound for Physiological Assessment of Coronary Stenosis
Authors: Atsushi Takagi, Yukio Tsurumi, Yasuhiro Ishii, Kazuhito Suzuki, Masatoshi Kawana, Hiroshi Kasanuki
Journal: Circulation (1999)

Background —Little is known regarding intravascular ultrasound (IVUS) criteria to determine the functional severity of coronary stenosis. Recently, fractional flow reserve (FFR) has emerged as a lesion-specific index of the functional severity of a coronary stenosis that is independent of systemic hemodynamic variability. The present study was undertaken to determine the IVUS parameters for the physiological severity of coronary stenosis. Methods and Results —Fifty-one lesions in 42 patients were evaluated by means of quantitative coronary angiogram, IVUS, and intracoronary pressure measurements. The FFR was calculated as the ratio of the distal coronary pressure divided by the proximal coronary pressure under hyperemia. We considered a value of the FFR &lt;0.75 as significant in determining inducible ischemia, according to the previous studies. The minimal luminal area (MLA) and the area stenosis were measured by IVUS. By regression analysis, the MLA showed a positive correlation with the FFR value ( r 2 =0.62, P &lt;0.0001). The area stenosis had a significant inverse correlation with the value of FFR ( r 2 =0.60, P &lt;0.0001). The IVUS thresholds that maximized the sensitivity and specificity were MLA &lt;3.0 mm 2 (sensitivity, 83.0%; specificity, 92.3%) and area stenosis &gt;0.6 (sensitivity, 92.0%; specificity, 88.5%). The combination of both criteria (MLA &lt;3.0 mm 2 and area stenosis &lt;0.6) without exception met a value of the FFR &lt;0.75. Conclusions —Anatomic parameters obtained by IVUS showed a significant correlation to the FFR values. The present study demonstrated that the combination of the MLA and area stenosis measured by IVUS can be an anatomic predictor for the physiological impact of coronary epicardial stenosis.
Choosing the best research design for each question
Authors: D. L Sackett, J. E Wennberg
Journal: BMJ (1997)

<b>Background:</b> Poor adherence is a key factor in poor asthma control. A connected inhaler system (CIS) comprising sensors on inhalers, a patient-facing app, and a Healthcare Professional (HCP) dashboard could improve asthma management by improving adherence. <b>Methods:</b> Study 207040 (NCT033800429) is one of the first to investigate the different elements of a CIS in improving adherence. The study had a 24-week, open-label, randomised, multi-centre, parallel group design with 5 treatment arms, in uncontrolled asthmatic patients [Asthma Control Test (ACT) &lt;20] on fixed dose ICS/LABA maintenance therapy. All participants (n=437) received fluticasone furoate/vilanterol Ellipta DPI maintenance therapy, and salbutamol MDI rescue therapy with Propeller Health® sensors attached. Participants were randomised to one of 5 treatment arms: data on (1) maintenance use to participant and HCP; (2) maintenance use to participant; (3) maintenance and rescue use to participant and HCP; (4) maintenance and rescue use to participant; or (5) no data to participant or HCP (control arm). <b>Results:</b> The primary endpoint was the effect of 6 months’ use of a CIS on adherence to maintenance therapy assessed over months 4-6, with the absolute adjusted mean adherence difference in arm 1 (data on maintenance to participant and HCP; 82.0%) being 13.2% (95% CI [6.3%, 20.0%]; p&lt;0.001) greater than arm 5 (control; 68.8%). For arms 2, 3 and 4 the adjusted mean differences were 9.0%, 9.8% and 8.9% respectively versus arm 5 (all statistically significant at the 5% level). <b>Conclusion:</b> The study demonstrates that a CIS can improve adherence to maintenance medication for patients with uncontrolled asthma. <b>Funding:</b> GlaxoSmithKline plc. (207040)
UN launches new action plan on maternal and child health
Authors: P. Moszynski
Journal: BMJ (2010)

The United Nations has pledged to focus on child and maternal health, as a new report says that nearly 0.5 million women die in childbirth each year and 3.6 million babies die in the first month of life.

The figures, presented at the New York launch of a campaign to improve maternal and child health, also showed that 5.2 million children die before the age of 5 years.

The UN secretary general, Ban Ki-moon, said, “Of all the millennium development goals maternal health has advanced the least and it is a key to all the rest. That is why, today, we are putting women’s and children’s health front and centre …
Elucidating the Role of IgM Memory B Cells in Common Variable Immunodeficiency
Authors: J.H. Park, C. Cunningham-Rundles
Journal: Journal of Allergy and Clinical Immunology (2012)

There is a very limited data on CD27+IgM+ B cells in CVID. Prior studies focused on their relation to bacterial pneumonia, but the precise role of these IgM memory B cells in CVID remains undefined, suggesting studies with broader objectives and a larger sample size. We therefore sought to elucidate the role of IgM memory B cells by characterizing immunological profiles and clinical parameters in a large cohort of CVID patients. Eighty-six CVID patients were divided into low vs normal IgM memory B cell groups using 9% as the cutoff. We analyzed immunological profiles and clinical parameters including history of recurrent pneumonia, anti-pneumococcal polysaccharide (anti-PnPS) IgG titers to 14 serotypes, lung CT scan findings, and associated non-infectious complications of CVID. In the low IgM memory B cell group (N=50), 72% experienced recurrent pneumonia, whereas only 28% did in the normal IgM memory B cell group (N=36), P<0.0001. Low IgM memory B cells were associated with lower number of switched memory B cells (<0.55% of B cells), P=0.04. Mean serum IgM level (32.9mg/dL vs 116.3mg/dL) and the mean number of protective anti-PnPS IgG titers (1.57 vs 2.95) were lower in low IgM memory B cell group (P=0.24 and P=0.18, respectively). There was no statistically significant difference in the incidence of non-infectious complications. Reduced IgM memory B cells are associated with higher incidence of pneumonia and lower numbers of switched memory B cells. Its measurement may help identify some CVID patients with greater risk of pneumonia.
Prolonged exposure of rat aorta to low levels of endotoxin in vitro results in impaired contractility. Association with vascular cytokine release.
Authors: T M McKenna
Journal: Journal of Clinical Investigation (1990)

Treatment of volunteers or animals with endotoxin in vivo results in reduced vascular reactivity to catecholamines. Endotoxin also causes liberation of the vasoactive cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF) from vascular smooth muscle and endothelial cells in culture. This study tested whether defects in contractility could be induced in isolated vascular tissue by prolonged exposure to endotoxin (1-100 ng/ml) in vitro, and whether IL-1 and TNF release by blood vessels is altered during the establishment of endotoxin induced contractile dysfunction. A concentration of endotoxin as low as 1 ng/ml suppressed contractions to norepinephrine (NE) and KCl; aortic sensitivity to NE also decreased. The presence of serum constituents or an intact endothelium were not necessary for endotoxin-induced vascular suppression. Aortas incubated with endotoxin liberated IL-1 and TNF in a dose-dependent fashion. The addition of dexamethasone or indomethacin during the incubations generally suppressed release of the cytokines and improved tissue reactivity to NE. The endotoxin-induced diminished vascular contraction and augmented IL-1 and TNF liberation required de novo protein synthesis; tissue incubated with endotoxin plus actinomycin D was completely shielded from the influence of endotoxin on vascular reactivity to NE. The association between endotoxin-induced vascular cytokine release and diminished contraction suggests a possible role for cytokines derived from the vasculature in the regulation of contractile function.
Thallium-201 Scintigraphy and Chemotherapeutic Response in Rhabdomyosarcoma
Authors: CARLO L. MAINI, ANNA TOFANI, ROSA SCIUTO, SILVIA CARPANO, MARCELLO CRECCO, CARLO MANNI, MASSIMO LOPEZ
Journal: Clinical Nuclear Medicine (1994)

Thallium-201 scintigraphy was used to evaluate chemotherapeutic response in a case of rhabdomyosarcoma treated with epirubicin. A scintigraphic semiquantitative index of tumor viability was correlated with MRI and clinical assessment. Both imaging studies were performed before therapy and after treatment involving a cumulative dose of 640 mg/m2 of epirubicin. A very good inverse correlation was observed between TI-201 uptake and tumor necrosis evaluated by MRI, leading to the conclusion that sequential TI-201 scintigraphy may have a role not only in delineating the extent of the tumor, but in objectively assessing tumor response to therapeutic interventions. The proposed scintigraphic method is much simpler to perform and less expensive than MRI-derived semiquantitative measurement of tumor necrosis.
Letter: In arduis fidelis.
Authors: D Hamilton
Journal: BMJ (1974)

20-month-old baby, who developed a roseolar rash at the same time.Among the types of virus isolated from throat or faecal specimens from my patients at the time of their roseolar reactions were adenovirus 2, 3, and 14, echovirus 9, 11, 27, and 30, Cox- sackie A6 and 9, Coxsackie B2, 4, and 5, and parainfluenza type 1.Most children who received the earlier, less attenuated, measles virus vaccines developed a roseolar reaction as their fever subsided.This rash differed from that of measles in two respects: it began on the trunk instead of the face and it appeared as the tempera- ture dropped and not at the start of the secondary fever.Children who undergo either the fast ("one-spike") or the slow (roseolar) febrile immunizing reaction are as a rule otherwise healthy and free from any localizing signs of infection in the ears, nose, throat, chest, abdomen, or urine.The younger the child, the higher is the temperature likely to be.Presumably the roseolar rash is due to virus particles being neutralized in the skin at the end of a period of viraemia.Perhaps viraemia does not occur in the "one-spike" fever and so no rash appears.Please may sixth disease now disappear from the next edition of textbooks?-Iam, etc., G. I.
Left bronchial isomerism associated with bronchomalacia, presenting with intractable wheeze.
Authors: P Lee, A Bush, J O Warner
Journal: Thorax (1991)

The cause of the Williams Campbell syndrome (bronchomalacia with bronchiectasis) is controversial. A boy with bronchomalacia, bifid ribs, and left bronchial isomerism presented with intractable wheeze mimicking asthma. The combination of the abdominal, bronchial, and atrial anatomy seen in this child has been described only once previously. The coexistence of these congenital abnormalities in this boy supports a congenital cause for the Williams Campbell syndrome. The need to assess wheezy children critically is emphasised.
The Current Status of Camptothecin Analogues as Antitumor Agents
Authors: W. J. Slichenmyer, E. K. Rowinsky, R. C. Donehower, S. H. Kaufmann
Journal: JNCI Journal of the National Cancer Institute (1993)

The nuclear enzyme topoisomerase I (topo I) has been recently recognized as the target for the anticancer drug camptothecin (CPT) and its derivatives. Two of the agents that target this enzyme—topotecan (TPT) and CPT-11—appear to be active against a broad range of human tumors. In the following presentation, we review 1) the role of topo I in normal cells, 2) the chemistry and proposed mechanism of action of CPT and its analogues, 3) the results of preclinical and clinical testing of TPT and CPT-11, and 4) mechanisms of resistance to these agents. In normal cells, topo I is thought to be involved in gene transcription and DNA replication. During the course of its normal catalytic cycle, topo I transiently forms a covalent bond with DNA. CPT and its derivatives slow the religation step of the enzyme and stabilize the covalent adduct between topo I and DNA. In S-phase cells, advancing replication forks convert these topo I-DNA adducts into double-strand breaks that appear to be responsible for the cytotoxicity of these agents. Preclinical studies demonstrate antineoplastic activity for TPT and CPT-11 in a variety of tumor models. Phase I studies have identified neutropenia as the dose-limiting toxicity for both drugs. Gastrointestinal effects might also be dose-limiting for CPT-11 administered on some schedules. CPT-11 has shown antitumor activity in phase II trials for patients with carcinomas of lung, cervix, ovary, colon, and rectum and for patients with non-Hodgkin's lymphoma. Phase II studies of TPT are in progress. Resistance to the cytotoxic effects of these agents might result from decreased production of topo I or from production of a mutated form of topo I. In addition, decreased metabolic activation of CPT-11 (which is a pro-drug) and active efflux of TPT by P-glycoprotein-mediated transport might contribute to resistance. As agents with a novel mechanism of action, tolerable toxicity, and encouraging antitumor activity in early clinical trials, TPT and CPT-11 are undergoing further clinical development. If these agents can be successfully combined with other active chemotherapy agents, the topo I-directed agents offer the potential for significant advances in the treatment of patients with a variety of malignancies. [J Natl Cancer Inst 85: 271–291, 1993]
Chondromalacia of the Patella Bone Imaging Correlated with Arthroscopic Findings
Authors: HARVEY S. KOHN, GARY N. GUTEN, B DAVID COLLIER, PURUSHOTHAM VELUVOLU, JOHN P. WHALEN
Journal: Clinical Nuclear Medicine (1988)

One hundred adult sports medicine patients with clinical findings suggesting chondromalacia of the patella underwent bone imaging. Of these patients, 50 eventually underwent arthroscopic surgery and the remaining 50 were treated conservatively. The intensity of abnormally increased scintigraphic activity in the patella correlated closely with the grade of chondromalacia observed by the arthroscopist. Bone imaging also was of value in directing the arthroscopist to clinically unsuspected torn menisci. In conclusion, for sports medicine patients with clinical findings suggestive of chondromalacia of the patella, bone imaging contributes to an accurate diagnosis and appropriate surgical planning.
Blockade of TGF-β action ameliorates renal dysfunction and histologic progression in anti-GBM nephritis
Authors: Aihua Zhou, Hikaru Ueno, Mayumi Shimomura, Ryojiro Tanaka, Toshiro Shirakawa, Hajime Nakamura, Masafumi Matsuo, Kazumoto Iijima
Journal: Kidney International (2003)