tbuckley/cabot-search huggingface dataset:
Immunologic and Neuropharmacologic Stimulation of Mucous Glycoprotein Release from Human Airways In Vitro
Authors: James H. Shelhamer, Zvi Marom, Michael Kaliner
Journal: Journal of Clinical Investigation (1980)

Human bronchial airways obtained after surgical resection were maintained in tissue culture for 24-48 h. Incorporation of [(3)H]- or [(14)C]-glucosamine, [(14)C]threonine, or Na(2)[(35)S]O(4) to the culture media resulted in biosynthesis of two radiolabeled glycoproteins-one filtering in the exclusion volume of Sepharose 2B, and the other filtering with an approximate molecular weight of 400,000. Both fractions had similar elution patterns from DEAE-cellulose anion exchange chromatography. [(3)H]Glucosamine was incorporated equally into the two fractions. The effects of anaphylaxis, histamine, and several neurohormones upon the release of [(3)H]glucosamine-labeled glycoproteins were analyzed, making no attempt to separate the two glycoprotein fractions. Three lines of evidence were found suggesting that mast-cell degranulation increases mucous release from cultured airways. (a) Supernatant fluids from anaphylaxed peripheral human lung that contained 200-400 ng/ml histamine and 400-1,000 U/ml slow-reacting substance of anaphylaxis (SRS-A) increased release by 40+/-18%. (b) The addition of antigen to IgE-sensitized airways led to the release of 26+/-7% of the total histamine and a 36+/-14% increase in mucous release. (c) Reversed anaphylaxis with anti-IgE antibodies induced a 36+/-6% release of histamine from the airways and an increase in the release of mucous glycoproteins of 25+/-9%. Exogenous histamine added to airways increased mucous glycoprotein release, an effect prevented by cimetidine, an H-2 antagonist. Selective histamine H-2, but not H-1 agonists increased mucous glycoprotein release, suggesting the possibility that anaphylaxis of airways results in increased mucous glycoprotein release partly through histamine H-2 stimulation.A cholinomimetic agonist, methacholine, increased mucous release; this response was prevented by atropine which alone had no effect. No response to beta-adrenergic stimulation with either isoproterenol or epinephrine was noted. However, alpha-adrenergic stimulation with either norepinephrine combined with propranolol or phenylephrine alone resulted in dose-related increases in glycoprotein release. Both alpha-adrenergic and cholinergic stimulation of human tissues induce the formation of guanosine 3',5'-phosphoric acid (cyclic GMP), and 8-bromo cyclic GMP added to the airways led to increased mucous secretion. Thus, it seems likely that neurohormones capable of stimulating cyclic GMP formation in human airways may lead to increased mucous glycoprotein release.
76 A MOLECULAR SIGNATURE AND ALGORITHM FOR THE DIAGNOSIS AND PROGNOSIS OF HEPATOCELLULAR TUMORS
Authors: J.-C. Nault, A. de Reyniès, G. Couchy, J. Tran Van Nhieu, T. Decaens, A. Laurent, D. Franco, J. Saric, J.-F. Blanc, C. Balabaud, P. Bioulac-Sage, P. Laurent-Puig, J. Zucman-Rossi
Journal: Journal of Hepatology (2011)
Renal ammonia and glutamine metabolism during liver insufficiency-induced hyperammonemia in the rat.
Authors: C H Dejong, N E Deutz, P B Soeters
Journal: Journal of Clinical Investigation (1993)

Renal glutamine uptake and subsequent urinary ammonia excretion could be an important alternative pathway of ammonia disposal from the body during liver failure (diminished urea synthesis), but this pathway has received little attention. Therefore, we investigated renal glutamine and ammonia metabolism in midly hyperammonemic, portacaval shunted rats and severely hyperammonemic rats with acute liver ischemia compared to their respective controls, to investigate whether renal ammonia disposal from the body is enhanced during hyperammonemia and to explore the limits of the pathway. Renal fluxes, urinary excretion, and renal tissue concentrations of amino acids and ammonia were measured 24 h after portacaval shunting, and 2, 4, and 6 h after liver ischemia induction and in the appropriate controls. Arterial ammonia increased to 247 +/- 22 microM after portacaval shunting compared to controls (51 +/- 8 microM) (P < 0.001) and increased to 934 +/- 54 microM during liver ischemia (P < 0.001). Arterial glutamine increased to 697 +/- 93 microM after portacaval shunting compared to controls (513 +/- 40 microM) (P < 0.01) and further increased to 3781 +/- 248 microM during liver ischemia (P < 0.001). In contrast to controls, in portacaval shunted rats the kidney net disposed ammonia from the body by diminishing renal venous ammonia release (from 267 +/- 33 to -49 +/- 59 nmol/100 g body wt per min) and enhancing urinary ammonia excretion from 113 +/- 24 to 305 +/- 52 nmol/100 g body wt per min (both P < 0.01). Renal glutamine uptake diminished in portacaval shunted rats compared to controls (-107 +/- 33 vs. -322 +/- 41 nmol/100 g body wt per min) (P < 0.01). However, during liver ischemia, net renal ammonia disposal from the body did not further increase (294 +/- 88 vs. 144 +/- 101 nmol/100 g body wt per min during portacaval shunting versus liver ischemia). Renal glutamine uptake was comparable in both hyperammonemic models. These results indicate that the rat kidney plays an important role in ammonia disposal during mild hyperammonemia. However, during severe liver insufficiency induced-hyperammonemia, ammonia disposal capacity appears to be exceeded.
Drug Addiction Prevention Program
Authors: Arnold J. Friedhoff
Journal: JAMA (1970)

To the Editor.—  As one of our programs in regard to drug addiction, we have attempted to develop a program of prevention. I should like to direct the attention ofJournalreaders to one of the means by which physicians can contribute to the prevention of this problem through the correct use of addictive agents. We have attempted to formulate the many cautions about addictive drugs into four simple principles so that they can be easily recalled. These principles are as follows.  First, use nonaddictive drugs whenever possible. For instance, antihistamines can often be substituted for barbiturates in the production of sedation.  Second, use the smallest possible effective dose of an addictive drug, inasmuch as larger doses increase the likelihood of physical dependence.  Third, maintain a level dose. The need for an increasing dose to obtain an effect is an indication of developing tolerance. If this occurs, treatment should be
Microregional Expression of Glucose Transporter-1 and Oxygenation Status: Lack of Correlation in Locally Advanced Cervical Cancers
Authors: Arnulf Mayer, Michael Höckel, Alexander Wree, Peter Vaupel
Journal: Clinical Cancer Research (2005)

Glucose transporter-1 (GLUT-1), a target gene of hypoxia-inducible factor-1, has been considered a candidate endogenous marker of tumor hypoxia. Expression of GLUT-1 may also serve as an indicator for the induction of the transcriptional response to hypoxia, which has been linked to enhanced proliferation, resistance to therapy, and metastatic propagation of cancer cells. Overexpression of GLUT-1 has been shown to correlate with poor prognosis in several tumor entities, among them cancers of the uterine cervix. The validity of these hypotheses is investigated.The expression of GLUT-1 was assessed in 80 biopsies of Eppendorf oxygenation measurement tracks from locally advanced cervical cancers in 47 patients using immunohistochemistry.No correlation was found between the expression of GLUT-1 and oxygenation variables (median pO2, HF 2.5 and HF 5). Expression of GLUT-1 was found greater in larger tumors (P = 0.0001) and to exhibit a linear increase with Federation Internationale de Gynecologie et d' Obstetrique stage (P = 0.002). Overall survival (P = 0.004) and recurrence-free survival (P = 0.007) were significantly shorter for patients with expression of GLUT-1. In the subgroup of patients treated with surgery, this effect on prognosis was not independent when pT stage or pN stage were included in a multivariate Cox proportional hazards model.The suitability of GLUT-1 as an endogenous marker of tumor hypoxia seems questionable. The association with prognosis may partially depend on confounding factors.
Abstract 4885: Changes of H3K9 modification by increased expression of HDAC2 and SUV39H1 modulates chromosome condensation in A549 lung cancer cells
Authors: Jin-Ah Park, Ae-Jin Kim, Joo-Kyung Lee, Myoung-Sun Ham, Keun-Cheol Kim
Journal: Cancer Research (2010)

Abstract Genetic information is condensed from interphasic chromatin to mitotic chromosome for correct segregation into two daughter cells. Phosphorylation of H3S10 is well-known as modification marker for chromosome condensation, but further modification at several histone residues could be required for correct mitosis. In this study, we show that H3K9me3 was dramatically increased at mitotic cells, whereas H3K9ac was decreased. Chromosome spreading analysis is shown that H3K9me3 was distinctly increased at a longitudinal section of chromosome at prophase and prometaphase. These combinational modification of H3K9 was resulted from the increased expression of HDAC2 and SUV39H1, suggesting that these proteins are involved in chromosome condensation. Interestingly, FACS analysis is shown that metaphasic progression was delayed in HDAC inhibition by TSA treatment. Moreover, HDAC2 expression was increased from late S phase to M phase, and SUV39H1 expression was sequentially followed from G2 to M phase, implicating that activities of HDAC2 and SUV39H1 are modulated during chromosome condensation. Therefore, we suggest that increased expression of HDAC2 and SUV39H1 facilitate chromosome condensation targeting combinational modification of H3K9. 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 4885.
Cystathionine β-synthase as a carbon monoxide-sensitive regulator of bile excretion
Authors: Tsunehiro Shintani, Takuya Iwabuchi, Tomoyoshi Soga, Yuichiro Kato, Takehiro Yamamoto, Naoharu Takano, Takako Hishiki, Yuki Ueno, Satsuki Ikeda, Tadayuki Sakuragawa, Kazuo Ishikawa, Nobuhito Goda, Yuko Kitagawa, Mayumi Kajimura, Kenji Matsumoto, Makoto Suematsu
Journal: Hepatology (2008)

Carbon monoxide (CO) is a stress-inducible gas generated by heme oxygenase (HO) eliciting adaptive responses against toxicants; however, mechanisms for its reception remain unknown. Serendipitous observation in metabolome analysis in CO-overproducing livers suggested roles of cystathionine beta-synthase (CBS) that rate-limits transsulfuration pathway and H(2)S generation, for the gas-responsive receptor. Studies using recombinant CBS indicated that CO binds to the prosthetic heme, stabilizing 6-coordinated CO-Fe(II)-histidine complex to block the activity, whereas nitric oxide (NO) forms 5-coordinated structure without inhibiting it. The CO-overproducing livers down-regulated H(2)S to stimulate HCO(3) (-)-dependent choleresis: these responses were attenuated by blocking HO or by donating H(2)S. Livers of heterozygous CBS knockout mice neither down-regulated H(2)S nor exhibited the choleresis while overproducing CO. In the mouse model of estradiol-induced cholestasis, CO overproduction by inducing HO-1 significantly improved the bile output through stimulating HCO(3) (-) excretion; such a choleretic response did not occur in the knockout mice.Results collected from metabolome analyses suggested that CBS serves as a CO-sensitive modulator of H(2)S to support biliary excretion, shedding light on a putative role of the enzyme for stress-elicited adaptive response against bile-dependent detoxification processes.
The No Endosonographic Detection of Tumor (NEST) Study: a Case Series of Pancreatic Cancers Missed on Endoscopic Ultrasonography
Authors: M. Bhutani, F. Gress, M. Giovannini, R. Erickson, M. Catalano, A. Chak, P. Deprez, D. Faigel, C. Nguyen
Journal: Endoscopy (2004)

Background and Study Aims: The purpose of this study was to identify possible associated factors that may have contributed to failure to detect a pancreatic neoplasm during endoscopic ultrasound (EUS) examinations by experienced endosonographers. Patients and Methods: A multicenter retrospective study was organized, and 20 cases of pancreatic neoplasms missed by nine experienced endosonographers were identified. Careful analysis of each case was carried out to identify the factors that might have led to the missed diagnosis on EUS. Results: Twelve patients with a missed pancreatic neoplasm had EUS features of chronic pancreatitis. Other factors that might have increased the likelihood of a false-negative EUS examination included a diffusely infiltrating carcinoma (n = 3), a prominent ventral/dorsal split (n = 2), and a recent episode (within the previous 4 weeks) of acute pancreatitis (n = 1). Five patients with a negative initial EUS underwent a follow-up EUS after 2-3 months, with a pancreatic mass being found in all cases. Three patients had a diffusely infiltrating pancreatic adenocarcinoma. Conclusions: EUS is not a foolproof method of detecting a pancreatic neoplasm. Possible associated factors that may increase the likelihood of a false-negative EUS examination include chronic pancreatitis, a diffusely infiltrating carcinoma, a prominent ventral/dorsal split and a recent episode (< 4 weeks) of acute pancreatitis. If there is a high clinical suspicion of pancreatic neoplasm, if EUS and other imaging methods are negative, and if the patient does not undergo surgery, this study suggests that a repeat EUS after 2-3 months may be useful for detecting an occult pancreatic neoplasm.
After period of failure, NHS regulator is now fit for purpose, say MPs
Authors: C. Dyer
Journal: BMJ (2014)

The Care Quality Commission, formerly “a case study in how not to run a regulator,” has turned itself around under new management and is now on the way to effective regulation of healthcare in England, says the House of Commons Health Committee.

The previous regime of hospital inspection was a “failure,” the MPs said, but they believed that the commission was now “ready to undertake a programme of substantial reform to develop and improve its regulatory functions.”

The CQC has undergone a complete reorganisation under its new chief executive, David Behan, and new chairman, David Prior. It has instituted longer, in-depth specialist hospital inspections under a new chief inspector of hospitals, Mike Richards, with teams including clinicians and patients inspecting against specified standards.

A damning report by the management consultancy firm Grant Thornton into the …
Applied Gynecologic Pathology.
Authors: Robert E. Scully
Journal: JAMA (1963)

The express aim of this volume is to stress the application of pathology to gynecologic disease for the benefit of medical students and clinicians. The author omits consideration of obstetric disorders, including ectopic pregnancy and abortion, even though these conditions are commonly encountered by the gynecologist. The text of approximately 160 pages is equally divided between clinical and pathological discussion, with over half the page space allotted to black and white photographs. The number of illustrations is excessive and their teaching value in many instances limited. Some of the gross photographs (eg, the 20 depicting the external and cut surfaces of various ovarian tumors) are much less informative than colorful word pictures might have been. The photomicrographs are generally of suboptimal quality, often repetitive in their aims and sometimes extravagantly disproportionate, in both size and number, to the related text. Thus, there are over six pages of photomicrographs of mixed
George E. Brown Memorial Lecture
Authors: HUGH MONTGOMERY
Journal: Circulation (1957)

It seems fair to say that prior to the use of the oxygen electrode there was a static concept of the oxygen tension of tissues. This was true in spite of the fact that Bazett and Sribyatta, with the gas bubble technic, had demonstrated one example of a labile oxygen tension, in the subcutaneous space of man. 17 They of course could not show the rapidity with which the changes take place. Experiments with the polarographic technic have shown that profound changes in oxygen tension can take place very rapidly, all the way from values approaching that of arterial blood down to zero. In vasodilated skin oxygen tension approaches that of arterial blood. When different concentrations of oxygen are breathed, the changes in oxygen tension in such skin closely follow those of the arterial blood. When the circulation to skin is limited by peripheral arterial occlusion, oxygen is reduced and does not increase on vasodilatation as much as does that of normal skin. When a normal person breathes oxygen, the oxygen in the tissues that use little oxygen quickly reaches a pressure 4 or 5 times that produced when he breathes air. In the case of tissues that use greater amounts of oxygen this relationship is not so close. The higher tensions have not been found in the tissues that use the most oxygen. The transfer of oxygen from the capillaries to the tissue is rapid but not instantaneous. The usual ranges of oxygen tension of various tissues such as skeletal muscle, heart muscle, brain, etc., are not yet known in terms of millimeters of mercury, but this should now be possible. It is hoped that local metabolisms will be measured reasonably accurately in intact tissues within the body. Perhaps the storage of oxygen by myoglobin and cytochromes can be derived, again in situ, from the metabolism and the rate of change of oxygen tension when the circulation is arrested. The potentialities of the oxygen electrode are great, but limitations of the method should be respected. Further development of the method may free it of some of its defects. Other methods may supplant it, but if so they will need to be equally rapid and more capable of exact calibration. In closing this presentation I want to thank our chairman, my friend Dr. Arthur Merrill, for allowing me to speak to you. I want also to thank Dr. George Brown, in memoriam, for his pioneering in the paths of study of the interrelations of circulatory and tissue physiology and medicine.
Specific oral tolerance induction with food in children: transient or persistent effect on food allergy?
Authors: C. Rolinck‐Werninghaus, U. Staden, A. Mehl, E. Hamelmann, K. Beyer, B. Niggemann
Journal: Allergy (2005)

Background: The standard treatment of food allergy is elimination of the incriminated food from the diet. Specific oral tolerance induction (SOTI) seems to be a promising approach for a causal treatment; however, it is unclear whether the tolerance achieved is transient or persistent. We report on a subset of three patients of a larger ongoing study who were treated successfully with SOTI treatment, but experienced a secondary loss of tolerance after a period of allergen avoidance. Methods: The patients suffered from IgE‐mediated allergy either to cow's milk (CM) (patient A) or hen's egg (HE) (patients B and C), confirmed by double‐blind, placebo‐controlled food challenge (DBPCFC). SOTI treatment was performed at home on a daily basis until tolerance to a maximum of 250 ml CM or 4.5 g lyophilized HE protein was achieved. The daily maintenance dose was 100 ml CM or 2.5 g HE protein. Results: Patients A, B and C reached tolerance to the maximum dose after 37, 41 and 52 weeks, respectively. According to the protocol, patients A and B performed a strict secondary elimination diet for 2 months prior to a follow‐up DBPCFC after a maintenance phase of 27 and 39 weeks, respectively. Patient C discontinued treatment for 2 days after 4 weeks on the maintenance dose. Despite previous tolerance, on re‐exposure to the allergen all patients experienced moderate systemic allergic reactions. Conclusions: We conclude that SOTI can induce transient tolerance in food allergy, but does not necessarily lead to its permanent abrogation. Regular allergen intake seems necessary to maintain the established tolerance.
Primary Arachnoid Cysts
Authors: L. C. Oliver
Journal: BMJ (1958)

Nine of these patients were sporadic but consecutive cases of clinically atypical pneumonia, of whom seven had an E.S.R. of over 90.mm. on admission and four had rates of 120 mm. or more at some stage of their illness.These levels are much higher than those com- monly seen in acute pneumonia.The high sedimentation rates are not due to the exces- sive aggregation of red cells produced by the cold agglu- tiiins.The plasma protein abnormalities which occur do not appear to be unusual or specific to this form of pneumonia.Such very high rates can be demonstrated only by the Westergren method; the Wintrobe method may give disproportionately low or even normal results.If a patient with acute uncomplicated pneumonia has an E.S.R. of over 90 mm. the diagnosis of primary atypical pneumonia should be considered, especially if there are any other unusual features.We are most grateful to Dr. Neville Oswald for his advice and to the physicians of St. Bartholomew's, the Royal Free, the Royal South Hants, and St. Thomas's Hospitals for their permission to iaclude details of patients who had been under their care.
Daphne Mary Pearson (née Yates)
Authors: I C Pearson, T C Pearson
Journal: BMJ (2006)

Former senior clinical medical officer in community paediatrics Richmond, Twickenham, and Roehampton Health Care Trust (b 1942; q Charing Cross Hospital, London, 1966; MA), died from primary glioma on 15 December 2005.

Daphne switched her career in general practice to community paediatrics when family life began in 1970. She also undertook family planning clinics and training and became an assistant forensic examiner. In 1989 she became full time senior clinical medical officer. In 1990 she had breast cancer but continued to work and then promote Breakthrough Breast Cancer for many years. On recovery she acted as consultant community paediatrician for three years, championing a multidisciplinary approach for children with disability. Aged 57, she successfully undertook an MA. She was determined yet philosophical when diagnosed as having a brain tumour and died 16 months later. She leaves a husband, Tom; three children; and four grandchildren.