tbuckley/cabot-search huggingface dataset:
Lymphocyte adhesion through very late antigen 4: evidence for a novel binding site in the alternatively spliced domain of vascular cell adhesion molecule 1 and an additional alpha 4 integrin counter-receptor on stimulated endothelium.
Authors: R H Vonderheide, T A Springer
Journal: The Journal of Experimental Medicine (1992)

Recent studies demonstrate that alternative splicing of mRNA from a single gene can produce two forms of vascular cell adhesion molecule 1 (VCAM-1): a six-immunoglobulin (Ig) domain form (VCAM-6D) and a seven-Ig domain form (VCAM-7D). Using a COS cell transient expression assay, we investigated whether VCAM-6D and VCAM-7D differ functionally in adhesion to the integrin VLA-4 (CD49d/CD29) on lymphoid cells. Binding of lymphoid cell lines and peripheral blood lymphocytes was completely blocked by VLA-4 monoclonal antibody (mAb) and one VCAM-1 mAb (4B9) to both VCAM-6D and VCAM-7D, whereas one VCAM-1 mAb (E1/6) completely blocked binding to VCAM-6D but only partially inhibited binding to VCAM-7D. We conclude that there is one VLA-4 binding site in the six Ig domains shared between VCAM-6D and VCAM-7D, and that the alternatively spliced domain 4 present in VCAM-7D provides a second VLA-4 binding site that is blocked by 4B9 but not the E1/6 mAb. We compared the inhibitory effects of anti-VCAM-1 and anti-VLA-4 mAbs on lymphoid cell adhesion to cultured human umbilical vein endothelial cells (HUVEC). The anti-VCAM-1 mAb 4B9 blocked the binding of PBL and lymphoid tumor cells to stimulated HUVEC better than the anti-VCAM-1 mAb E1/6. Because VCAM-7D is the predominant form of VCAM-1 expressed by stimulated endothelial cells, this difference in VCAM-1 mAb inhibition is attributed to lymphoid cell binding to VCAM-7D on stimulated HUVEC. Although the anti-VLA-4 mAb and anti-VCAM-1 mAb 4B9 equally inhibited PBL binding to stimulated HUVEC, mAb 4B9 inhibited the binding of two lymphoid cell lines significantly less than anti-VLA-4 mAb. Combination of 4B9 mAb with function-blocking antiserum to human fibronectin, a second known ligand for VLA-4, also failed to inhibit as much as anti-VLA-4 mAb. These findings suggest that adhesion of lymphoid cell lines through VLA-4 or other alpha 4 integrins may involve inducible counter-receptor(s) on endothelium distinct from either VCAM-1 or fibronectin. Time course experiments indicate that the fraction of alpha 4 integrin-dependent binding that can be blocked by anti-VCAM-1 mAb E1/6 rises and peaks within 2 h of tumor necrosis factor (TNF) stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Ampicillin-Resistant Shigella sonnei
Authors: Richard C. Tilton
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The article of Ross et al (221:45, 1972) points out apparent geographic differences in the distribution of ampicillin-resistant shigellae; observed 3.7% from 1967 to 1970 in Atlanta as contrasted with his own survey, which shows an increase to 95% ampicillin resistance in 1971. From 1968 to May 1971, approximately 95% of all<i>Shigella</i>species isolated from clinical specimens at the University of Connecticut hospital were susceptible to ampicillin as measured by disc diffusion techniques. From May 1971 to December 1971, there were 25 individual isolations of<i>Shigella sonnei;</i>three were resistant to ampicillin. From January 1972 to the present, there have been 49 separate isolations of<i>Shigella sonnei</i>of which 40 were resistant to ampicillin (81% resistance). All of the ampicillinresistant strains were also resistant to sulfonamide, tetracycline, and streptomycin. Minimum inhibitory concentrations (MIC) were performed on all ampicillin-resistant<i>Shigella sonnei</i>isolates and were found to be
Hypoalbuminaemia and coeliac disease
Authors: V Tan, D Stella, H Frydenberg, C Mow, S Nandurkar, P R Gibson
Journal: Gut (2008)

A 23-year-old woman was diagnosed with coeliac disease with positive serology and typical duodenal histology. A gluten-free diet was instituted. About 9 months later, she presented with bipedal oedema that developed overnight, associated with a fall in …
Complications of the arrested primary histoplasmic complex
Authors: B. Felson
Journal: JAMA (1976)

THE GAMUT of clinically active and symptomatic histoplasmosis has become well known, especially in endemic areas. Manifestations such as disseminated forms, active histoplasmoma in the young adult, and cavitary pulmonary disease in elderly men are well-recognized syndromes. Less attention has been focused on mechanically induced (noninfectious) complications related to healing or arrested primary infection. Such complications presented here include simple and complicated broncholithiasis, bronchial compression with resulting atelectasis or bronchiectasis, fistula formation from mediastinal lymph nodes, superior vena cava syndrome, and giant mediastinal cyst. <h3>Diagnosis</h3> The presence of<i>Histoplasma capsulatum</i>was established (primarily by microscopy) in the following cases from surgical or autopsy specimens, except in patients 1 and 2 in whom roentgenographic and serologic evidence strongly indicated the diagnosis. <h3>Giant Cyst of the Mediastinum.—</h3> Caseous lymphadenitis during primary infection with<i>H capsulatum</i>is common in the lymph nodes that drain the primary lung lesion. The extent of involvement and
Tetracycline Toxicity in Pregnancy
Authors: Peggy J. Whalley, Reuben H. Adams, Burton Combes
Journal: JAMA (1964)

Severe liver and pancreatic dysfunction were observed in five obstetrical patients treated for pyelonephritis. One patient died. These complications are believed due to tetracycline toxicity on the basis of clinical features of the illness, the characteristic appearance of liver biopsies, and quantitative analyses of sera indicating that unusually high levels of tetracycline were present during therapy. Pregnancy and pyelonephritis appear to be important factors in the genesis of these complications. Our patients closely resemble those in reported cases of obstetrical acute yellow atrophy, a disorder of unknown etiology. It is suggested that this latter clinical syndrome may result from various etiological factors, including drugs, one of which is tetracycline.
Sleep Apnea and Hypertension: A Population-based Study
Authors: Khin Mae Hla
Journal: Annals of Internal Medicine (1994)

Objective: To measure the independent association of sleep-disordered breathing (sleep apnea and habitual snoring) and hypertension in a healthy adult population. Design: A cross-sectional study of blood pressure during wakefulness and sleep among participants with and without sleep-disordered breathing. Setting: Community-based study. Participants: 147 men and women, aged 30 to 60 years, selected from Wisconsin State employees enrolled in the Wisconsin Sleep Cohort Study, an ongoing, prospective, epidemiologic study of sleep-disordered breathing. Measurements: Sleep and medical history interview, nocturnal polysomnography, and 24-hour ambulatory blood pressure monitoring in all participants. Results: Mean blood pressures were significantly higher among participants with sleep apnea (≥ 5 apneas or hypopneas per hour of sleep) compared with those without (131/80 ±1.7/1.1 mm Hg compared with 122/75 ±1.9/1.2 mm Hg during wakefulness and 113/66 ±1.8/1.1 mm Hg compared with 104/62 ±2/1.3 mm Hg during sleep, respectively; P < 0.05). The variability of the blood pressure during sleep was significantly greater in participants with sleep apnea or a history of snoring compared with those without (P < 0.05). After controlling for obesity, age, and sex, sleep apnea was significantly associated with hypertension in a dose-response fashion, with odds ratios ranging from 2.0 for 5 apneic or hypopneic episodes per hour of sleep to 5.0 for 25 apneic or hypopneic episodes. Conclusions: Our data indicate an association between hypertension and sleep apnea independent of obesity, age, and sex in a nonselected, community-based adult population.
Endothelium-derived relaxing factor inhibits transport and increases cGMP content in cultured mouse cortical collecting duct cells.
Authors: B A Stoos, O A Carretero, R D Farhy, G Scicli, J L Garvin
Journal: Journal of Clinical Investigation (1992)

Stimulation of the release of endothelium-derived relaxing factor (EDRF) in the kidney has been shown to result in natriuresis without affecting glomerular filtration rate. This may be due to EDRF directly regulating solute transport in the cortical collecting duct (CCD). To test this hypothesis, we measured the effect of bradykinin (Bk) or acetylcholine (Ach) on short-circuit current (Isc; a measure of active transport) in a CCD cell line (M-1), in the presence or absence of cow pulmonary artery endothelial (CPAE) cells. 10(-9) M Bk or 10(-7) M Ach had no effect on M-1 Isc in which CPAE cells were absent. The addition of CPAE cells to M-1 cells also did not affect M-1 Isc. On the other hand, when 10(-9) M Bk or 10(-7) M Ach were added to M-1 cells in the presence of CPAE cells, Isc decreased from 43 +/- 4.5 to 26 +/- 4 and 64 +/- 9 to 33 +/- 4 microA/cm2, respectively (P less than 0.001). Nitroarginine (N-Arg, 10(-4) M), a competitive inhibitor of EDRF production, blocked the inhibition in M-1 Isc due to both agonists. Since cGMP is the second messenger of EDRF in vascular smooth muscle, we measured the effects of Bk on cGMP production in M-1 cells in the presence and absence of CPAE cells. Bk increased cGMP content in M-1 cells in the presence of CPAE cells from 33 +/- 3.4 to 132 +/- 11.7 fmol/10(6) M-1 cells (P less than 0.001). When cultures of M-1 and CPAE cells were treated with N-Arg and challenged with Bk, Bk's effect on cGMP was partially blocked (61.4 +/- 12 fmol/10(-6) M-1 cells; NS). These data suggest that EDRF inhibits transport and increases cGMP content in M-1 cells.
Biology of Progesterone Receptor Loss in Breast Cancer and Its Implications for Endocrine Therapy
Authors: Xiaojiang Cui, Rachel Schiff, Grazia Arpino, C. Kent Osborne, Adrian V. Lee
Journal: Journal of Clinical Oncology (2005)

The response to endocrine therapy in breast cancer correlates with estrogen receptor (ER) and progesterone receptor (PR) status. ER-positive/PR-negative breast cancers respond less well to selective ER modulator (SERM) therapy than ER-positive/PR-positive tumors. The predictive value of PR has long been attributed to the dependence of PR expression on ER activity, with the absence of PR reflecting a nonfunctional ER and resistance to hormonal therapy. However, recent clinical and laboratory evidence suggests that ER-positive/PR-negative breast cancers may be specifically resistant to SERMs, whereas they may be less resistant to estrogen withdrawal therapy with aromatase inhibitors, which is a result inconsistent with the nonfunctional ER theory. Novel alternative molecular mechanisms potentially explaining SERM resistance in ER-positive/PR-negative tumors have been suggested by recent experimental indications that growth factors may downregulate PR levels. Thus, the absence of PR may not simply indicate a lack of ER activity, but rather may reflect hyperactive cross talk between ER and growth factor signaling pathways that downregulate PR even as they activate other ER functions. Therefore, ER-positive/PR-negative breast tumors might best be treated by completely blocking ER action via estrogen withdrawal with aromatase inhibitors, by targeted ER degradation, or by combined therapy targeting both ER and growth factor signaling pathways. In this review, we will discuss the biology and etiology of ER-positive/PR-negative breast cancer, highlighting recent data on molecular cross talk between ER and growth factor signaling pathways and demonstrating how PR might be a useful marker of these activities. Finally, we will consider the clinical implications of these observations.
THE REGENERATIVE CYCLE OF MOTONEURONS, WITH SPECIAL REFERENCE TO PHOSPHATASE ACTIVITY
Authors: David Bodian, Robert C. Mellors
Journal: The Journal of Experimental Medicine (1945)

1. The regenerative cycle of motoneurons after axon amputation is described, and an attempt made to correlate morphological and chemical events in cell bodies with the growth requirements of regenerating axons. 2. The "normal" pattern of Nissl material in the cell is considered to be the resultant of a steady state in cytoplasmic nucleoprotein. Chromatol is then interpreted as a shift of the balance of nucleoprotein turnover in fa of degradation. The rapid early depletion of Nissl substance in chromatolysis is ascribed to the increased growth requirements created by the active early sprouting of the regenerating axon. Acid phosphatase activity begins to increase above normal levels during this period in the region of nucleopro degradation. 3. The recovery period of chromatolysis due to axon section coincide in time with the phase of gradual lengthening of the regenerating axon, and is thought to represent a gradual restoration of the balance of nucleoprotein degradation and synthesis. During this period acid phosphatase activity is at its height in the region of transformation of Nissl substance, later declines to normal levels when the original pattern of Nissl bodie is restored. 4. The transformation of cytoplasmic nucleoprotein which occurs in chromatolysis after axon section, with the probable liberation (46), and depletion (44), of nucleotides, associated with acid phosphatase activity, suggests the hypothesis that liberated nucleotides or nucleotide compounds may pass down the axon in which they take part in enzymatic activity associated with growth and organization of the newly formed axon. This type of activity would not be incompatible with the ideas previously expressed (30, 81) of a continual function of Nissl substance in maintaining the integrity of the large volume of cytoplasm represented by the axon, as well perhaps as the associated myelin sheath.
Cardiovascular Effects of Cimetidine
Authors: GEORGE NIKOLIC
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 February 1983Cardiovascular Effects of CimetidineGEORGE NIKOLIC, M.B., B.S.GEORGE NIKOLIC, M.B., B.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-2-258_5 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The cardiovascular effects of Cimetidine have never been documented through organized studies addressing this problem; the number of case reports describing them may merely reflect the widespread use and abuse of the drug (1). Contrary to the claim of Freston in his recent review (2) there are, however, some reports of adverse cardiac reactions after oral use of Cimetidine in patients without heart disease (3, 4). Like others, these reports do not unequivocally incriminate Cimetidine for the findings observed.From a cardiologist's point of view, the important cardiovascular effects of Cimetidine are related to its interaction with...References1. SCHADEDONALDSON RR. HOW physicians use Cimetidine. N Engl J Med. 1981;304:1281-4. CrossrefMedlineGoogle Scholar2. FRESTON J. Cimetidine: II. Adverse reactions and patterns of use. Ann Intern Med. 1982;97:728-34. LinkGoogle Scholar3. KING A. Cardiac arrest and Cimetidine [Letter]. Med J Aust. 1981;1:139-40. CrossrefMedlineGoogle Scholar4. HISSHEPLERFALKOWSKISUNSHINE JBAI. Fatal bradycardia after intentional overdose of Cimetidine and diazepam [Letter]. Lancet. 1982;2:982. CrossrefMedlineGoogle Scholar5. SOMOGYIHEINZOW AB. Cimetidine reduces procainamide elimination [Letter]. N Engl J Med. 1982;307:1080. CrossrefMedlineGoogle Scholar6. NIKOLICSINGH GJ. Cimetidine, vasopressin and chronotropic incompetence. Med J Aust. 1982;2:435-6. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCardiovascular Effects of CimetidineGlDEN KOREN, M.D. 1 February 1983Volume 98, Issue 2Page: 258-259KeywordsAdverse reactionsCardiovascular therapyDrug abuseDrugsHeart diseases Issue Published: 1 February 1983 PDF DownloadLoading ...
Stretch-dependent calcium uptake associated with myogenic tone in rabbit facial vein.
Authors: I Laher, C van Breemen, J A Bevan
Journal: Circulation Research (1988)

Many blood vessels possess stretch-dependent myogenic tone. This tone contributes to the active resistance in small arteries, which regulates blood flow in the body. In this report we describe results indicating that stretch-dependent myogenic tone in the rabbit facial vein, a vascular preparation with useful experimental properties, is accompanied by an increased uptake of 45Ca2+. This influx may not occur through voltage-gated Ca2+ channels, since neither the extent of myogenic tone nor 45Ca2+ influx is affected by a concentration of 1,4-dihydropyridine (PN 200-110, 10 nM) that reduces tone and 45Ca2+ influx due to the depolarization by K+. These results indicate that in myogenically active vessels a stretch-activated influx of Ca2+ may occur through distinct Ca2+-entry pathways.
Buccal Nitroglycerin Tablets in Heart Failure
Authors: AVIJIT LAHIRI
Journal: Annals of Internal Medicine (1986)

ExcerptTo the editor: A recent letter reported the application of nitroglycerin ointment to the buccal mucosa for relieving refractory pulmonary oedema (1). Sublingual nitroglycerin has also been used for the management of pulmonary oedema, and a comparative study of intravenous isosorbide dinitrate with furosemide has shown a better haemodynamic profile with nitrates in the management of acute heart failure occurring after infarction. Although buccal nitroglycerin ointment may have a prompt effect on left ventricular function, proper dose regulation may be difficult. Buccal-release nitroglycerin tablets which produce both rapid and sustained release of nitroglycerin are now available (2). We report here...
CLINICAL OUTCOME AND SENSITIVE TROPONIN I ASSAY IN PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME
Authors: Nicholas L. Mills, Antonia MD Churchhouse, Atul Anand, David Gamble, Margaret MacLeod, Catriona Graham, Simon Walker, Martin Denvir, Keith AA Fox, David E. Newby
Journal: Journal of the American College of Cardiology (2010)
Heat-killed Corynebacterium parvum enhances endotoxin lung injury with increased TNF production in guinea pigs.
Authors: S Tasaka, A Ishizaka, K Sayama, F Sakamaki, H Nakamura, T Terashima, Y Waki, K Soejima, M Nakamura, H Matsubara, S Fujishima, M Kanazawa
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Corynebacterium parvum (CP) is known to increase susceptibility to endotoxin, which is associated with increased production of tumor necrosis factor (TNF). We investigated the effect of CP-priming on the pathogenesis of acute lung injury caused by intratracheal Escherichia coli endotoxin (lipopolysaccharide [LPS]). Guinea pigs were divided into four groups: (1) control (n=6), (2) CP-alone (n=6), (3) LPS-alone (n=6) and (4) CP + LPS (n=6). A CP dose of 4 mg/kg was injected intraperitoneally 7 d before the study. Animals were observed for 4 h after intratracheal administration of 0.02 mg/kg of LPS. The lung wet-to-dry weight ratio (W/D), [125I] albumin concentration ratio of lung tissue to plasma (T/P) and of bronchoalveolar lavage (BAL) fluid to plasma (B/P) and differential cell count in BAL fluid were examined. In the LPS-alone group, neither excess lung water nor increased albumin leakage was observed. The CP + LPS group showed increased lung water and albumin leakage as compared with the other three groups (p<0.05). We also observed increased cell counts in BAL fluid (p<0.05), in the CP + LPS group. The spleen weight was increased in guinea pigs pretreated with CP, indicating reticuloendothelial system (RES) activation. In the CP + LPS group, the TNF level was increased in both plasma and BAL fluid. We conclude that pretreatment with CP enhances LPS-induced acute lung injury in parallel with increasing TNF production, which suggests that the activation of mononuclear phagocytes contributes to increased susceptibility to intratracheal endotoxin in guinea pigs.
A retrospective study of outcome for patients referred for oesophageal studies from a district general hospital respiratory clinic
Authors: B. Ebert, K. Noble, S. Vathenen, D. Brocklebank, H. Abusriwil, D. Aldulaimi
Journal: Gut (2011)

<h3>Introduction</h3> Oesophageal manometry and pH studies can be used to evaluate patients with atypical reflux symptoms, such as chronic cough, or recurrent chest infections, bronchiectasis and pulmonary fibrosis. Patients with demonstrated reflux that fail to respond to PPI therapy may be considered for antireflux surgery. Few studies have reported outcomes for patients referred for oesophageal studies from respiratory clinics based in district general hospitals. <h3>Methods</h3> We retrospectively identified and reviewed the records of all patients referred from a general respiratory clinic for oesophageal manometry and pH studies. <h3>Results</h3> 112 patients were referred for oesophageal pH studies from respiratory clinic. The most common presenting symptom was cough (63 patients), other indications included recurrent chest infections (26), bronchiectasis (23) and pulmonary fibrosis (9). 110 patients tolerated the procedure; 74 patients (67.3%) were found to have significant acid reflux. 33 patients were referred for surgical opinion. Reasons not to refer included patient refusal, poor lung function, obesity and resolution of symptoms. 25 patients had antireflux surgery. 30% of patients reported an improvement or resolution of symptoms post surgery. <h3>Conclusion</h3> Oesophageal studies and antireflux surgery are of benefit to a significant proportion of carefully selected patients from routine respiratory clinics.
Comparison of methods to identify individuals at increased risk of coronary disease from the general population
Authors: S Wilson
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b> To evaluate the guidelines on measurement of cholesterol in the national service framework for coronary heart disease and to compare alternative strategies for identifying people at high risk of coronary disease in the general population. <b>Design</b> Comparison of methods (national service framework criteria, Sheffield tables, age threshold of 50 years, estimated risk assessment using fixed cholesterol values) for identifying people with a 10 year coronary event risk of 15% or greater. <b>Setting</b> Health survey for England 1998. <b>Subjects</b> 6307 people aged between 30 and 74 years with no history of myocardial infarction, stroke, or angina. <b>Main outcome measures</b> Proportion of the total population selected for measurement of cholesterol and proportion of people at 15% or greater risk identified. <b>Results</b> The national service framework guidelines selected 43.4% (95% confidence interval 42.2% to 44.6%) of the study population for cholesterol measurement and identified 81.2% (80.2% to 82.2%) of those at 15% or greater risk. The Sheffield tables selected 73.1% (72.0% to 74.2%) for cholesterol measurement and identified 99.91% (99.83% to 99.99%) of those at 15% or greater risk. An age threshold of 50 years selected 46.3% (45.1% to 47.5%) for cholesterol measurement and identified 92.8% (92.1% to 93.4%) of those at 15% or greater risk. Estimated risk assessments using fixed cholesterol values selected 17.8% (16.8% to 18.7%) for cholesterol measurement and identified 75.9% (74.8% to 76.9%) of those at 15% or greater risk. <b>Conclusion</b> Measuring the cholesterol concentration of everyone aged 50 years and over is a simple and efficient method of identifying people at high risk of coronary disease in the general population.