tbuckley/cabot-search huggingface dataset:
Plasma content of B6 vitamers and its relationship to hepatic vitamin B6 metabolism.
Authors: L Lumeng, A Lui, T K Li
Journal: Journal of Clinical Investigation (1980)

The plasma content of B6 vitamers is governed by, among other factors, dietary supply and metabolic interconversion. This study examines the effect of pyridoxine supplementation on the plasma content of B6 vitamers and pyridoxic acid in man, and the metabolic conversion and release of B6 compounds in isolated rat hepatocytes. Six healthy human subjects were given 100 mg pyridoxine-HCl/d orally for 1--3 wk. Before pyridoxine supplementation, the mean total plasma level of B6 vitamers was 114 +/- 9 nM; and pyridoxal-P, pyridoxamine-P, pyridoxal, pyridoxine, and pyridoxamine accounted for 54, 3, 11, 27, and 5%, respectively. Plasma level of pyridoxic acid was 40 +/- 7 nM. Thus, pyridoxal-P is the principal B6 vitamer in plasma. During pyridoxine supplementation, mean plasma levels of the B6 vitamers and pyridoxic acid increased to 655 +/- 122 and 222 +/- 55 nM, respectively. The plasma content of pyridoxal-P and pyridoxic acid increased 6--7-fold and that of pyridoxal, 12-fold, but the pyridoxine level did not increase. Isolated hepatocytes, 1 g/15 ml, were incubated for 2 h with 3.33 microM [14C]pyridoxine (6 microCi/mumol). At zero time, the cells contained about 35 nmol pyridoxal-P and 25 nmol pyridoxamine-P. After 2 h incubation, the cellular content of pyridoxal-P and pyridoxamine-P did not change significantly, but the medium contained 5.9 nmol pyridoxal-P, 0.3 nmol pyridoxamine-P, 7.2 nmol pyridoxal, 26.6 nmol pyridoxine, 0.3 nmol pyridoxamine, and 7.5 nmol pyridoxic acid. Whereas the specific radioactivity of pyridoxal-P, pyridoxal, and pyridoxic acid in the medium approached that of [14C]pyridoxine, the specific radioactivity of cellular pyridoxal-P and pyridoxamine-P was only 20% of that of pyridoxine. Thus, newly synthesized pyridoxal-P is not freely exchangeable with endogenous pyridoxal-P, but is preferentially released or degraded to pyridoxal and pyridoxic acid. The latter B6 compounds are also released. These results suggest that orally ingested pyridoxine is rapidly metabolized in liver and its products are released into the circulation in the form of pyridoxal-P, pyridoxal, and pyridoxic acid.
The Cambridge Illustrated History of Medicine
Authors: David J. Rothman
Journal: Annals of Internal Medicine (1998)

Medical Writings1 March 1998The Cambridge Illustrated History of MedicineDavid J. Rothman, PhDDavid J. Rothman, PhDColumbia College of Physicians and Surgeons, New York, New YorkSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-5-199803010-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Porter R; ed. 400 pages. New York: Cambridge Univ Pr; 1996. $39.95. ISBN 0521442117. Order phone 800-872-7423.Field of medicine: History of medicine.Format: Hardcover book.Audience: Educated laypersons and interested physicians.Purpose: To present a survey of western medicine.Content: Edited by the distinguished English historian Roy Porter, this is a lavishly presented and clearly narrated account of the major transformations that mark the rise and course of western scientific medicine. It covers a wide range of subjects, including the history of modern diseases, medical pioneers, and therapeutic discoveries.Highlights: The opening chapters on the history of disease and ... Author, Article, and Disclosure InformationAffiliations: Columbia College of Physicians and Surgeons, New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFrom Ancient Texts to Digital Imagery: A Brief History on the Evolution of Anatomic Illustrations 1 March 1998Volume 128, Issue 5Page: 415-416KeywordsHand strengthHealth care policyHeartHistory of medicineHospital medicineSurgeonsSurgery ePublished: 15 August 2000 Issue Published: 1 March 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 2691: A randomized Phase III study comparing the efficacy of Bacillus Calmette Guérin strain Tice versus Connaught for immunotherapy of non-muscle invasive bladder cancer
Authors: Cyrill A. Rentsch, Frédéric Birkhäuser, Urs E. Studer, Matthew L. Albert, George N. Thalmann
Journal: Cancer Research (2012)

Abstract Introduction: For almost forty years now, adjuvant immunotherapy with intravesical Bacillus Calmette Guérin (BCG) is standard of care in the treatment of non-muscle invasive bladder cancer (NMIBC). The question whether the choice of the different available BCG strains used for treatment influences treatment outcome is still under debate. We report on a randomized phase III study comparing the two most commonly used strains in Europe and the USA. Patients and Methods: This study was performed under approval of the Cantonal Ethical Committee of Bern, Switzerland, to evaluate recurrence free survival in patients treated with BCG as the primary end-point. Between 1998 and 2010 149 patients (n=149) were recruited. Patients underwent transurethral resection of all visible bladder tumors or random bladder biopsies in case of a solely positive bladder wash cytology. TaG3 and T1G3 tumors underwent a second resection to confirm non-muscle invasive disease. Two to 15 days after surgery, patients were either randomized to receive six weekly intravesical instillations with 2-8x108 CFU OncoTice ® (BCG Tice) or 6.6-19.2 x108 CFU ImmuCyst ® (BCG Connaught) dissolved in 50 ml of saline according to manufacturers recommendations. Patients were followed in 3-monthly intervals for 3yrs, then in 6-monthly intervals by cystoscopy and bladder wash cytology. Relapses were confirmed by histology after transurethral surgery. Cox regression analysis and Log rank tests served for statistical analysis. Results: Gender, age, tumor stage and grade were well balanced between the two treatment arms (p=0.38). Median follow up was 25 months (range: 0.3-136). Side effects did not differ between the two treatment arms (p=0.42). Age and gender did not have an impact on treatment response (p=0.71). Five year recurrence-free survival for all patients was 61%. Patients treated with Connaught had significantly less recurrences than patients treated with OncoTice (p&amp;lt;0.002). Five year recurrence-free survival was 75% and 46% for Connaught and Tice treated patients, respectively. Median recurrence-free survival was 28 months (range: 0.6-136) for Connaught and 22 months (range: 0.3-122) for Tice treated patients. Progression-free and overall survivals were not significantly different between the two treatment arms. Conclusions: The choice of the BCG strain impacts on treatment outcome and favors the use of BCG Connaught over Tice in the treatment of NMIBC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2691. doi:1538-7445.AM2012-2691
GSK confirms probe by Chinese authorities
Authors: J. Parry
Journal: BMJ (2013)

A group of senior executives at GlaxoSmithKline is at the centre of an investigation by Chinese authorities into the company’s operations in China.

Managers from each of the UK based drug firm’s three sites in Beijing, Changsha, and Shanghai are believed to be in police custody, report the official news agency Xinhua and the Hong Kong newspaper South China Morning Post .

A …
The problem with BEAUTY: a medical librarian's perspective
Authors: F. King
Journal: BMJ (2015)

I strongly disagree with one of Pottegard and colleagues’ BEAUTY criteria for the standardised assessment of acronym quality: five points if the acronym is a real word.1 From a medical librarian’s point of view, real words as clinical trial names—especially real words commonly used in medicine—make clinical trials very difficult to find in Medline and other databases.

Take, for …
Corrigendum to “SPIO-PICsome: Development of a highly sensitive and stealth-capable MRI nano-agent for tumor detection using SPIO-loaded unilamellar polyion complex vesicles (PICsomes)” [J. Control. Release, Volume 169 (2013) 220–227]
Authors: Daisuke Kokuryo, Yasutaka Anraku, Akihiro Kishimura, Sayaka Tanaka, Mitsunobu R. Kano, Jeff Kershaw, Nobuhiro Nishiyama, Tsuneo Saga, Ichio Aoki, Kazunori Kataoka
Journal: Journal of Controlled Release (2014)
Belittlement and harassment of medical students: Seems to achieve focus
Authors: Jonathan D Belsey
Journal: BMJ (2006)

EDITOR—Until recently I would have disagreed with Aref-Adib,1 but now I am inclined to agree. Last summer I was involved in the production of a BBC programme Thoroughly Modern Medic , in which six third year medical students were subjected to a week of 1950s' style ward based teaching. In essence, we subjected them to a traditional …
Expression of adhesion molecules and chemotactic cytokines in cultured human mesothelial cells.
Authors: N Jonjić, G Peri, S Bernasconi, F L Sciacca, F Colotta, P Pelicci, L Lanfrancone, A Mantovani
Journal: The Journal of Experimental Medicine (1992)

The mesothelium is a flat epithelial lining of serous cavities that could gate the traffic of molecules and cells between the circulation and these body compartments. The present study was designed to elucidate the capacity of mesothelial cells to express adhesion molecules and chemoattractant cytokines, two fundamental mechanisms of regulation of leukocyte recruitment. Cultured human mesothelial cells express appreciable levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and these were increased by in vitro exposure to tumor necrosis factor (TNF), interferon gamma (IFN-gamma), or TNF and IFN-gamma. Interleukin 1 (IL-1) was a less consistent stimulus for adhesion molecule expression in vitro. Unlike endothelial cells, used as a reference cell population, resting or stimulated mesothelial cells did not express E-selectin and ICAM-2, as assessed by flow cytometry. Analysis of VCAM-1 mRNA by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that mesothelial cells expressed both the seven- and the six-Ig domain transcripts, with predominance of the longer species. Monocytes bound appreciably to "resting" and, to a greater extent, to stimulated mesothelial cells. Monocytes exposed to IFN-gamma and lipopolysaccharide, used as prototypic activation signals, showed increased capacity to bind mesothelial cells. Anti-CD18 monoclonal antibody significantly inhibited binding of monocytes to mesothelial cells, and this blocking effect was amplified by anti-very late antigen 4. Mesothelial cells were able to express the chemotactic cytokines IL-8 and monocyte chemotactic protein 1 at the mRNA and protein levels. These results indicate that mesothelial cells can express a set of adhesion molecules (ICAM-1 and VCAM-1) overlapping with, but distinct from, that expressed in vascular endothelium (ICAM-1, ICAM-2, VCAM-1, E-selectin), and that these are functionally relevant for interacting with mononuclear phagocytes. The regulated expression of adhesion molecules and chemotactic cytokines by mesothelial cells is probably important in inflammatory and immune reactions that involve serous cavities, such as the long-known macrophage appearance and disappearance reactions.
Oral Administration of Vancomycin in the Treatment of Staphylococcal Enterocolitis
Authors: James F. Wallace, Ronald H. Smith, Robert G. Petersdorf
Journal: New England Journal of Medicine (1965)

VANCOMYCIN is a bactericidal antibiotic that has been highly effective in the treatment of infections caused by staphylococci resistant to penicillin G.1 , 2 Difficulties associated with parenteral administration of this drug, notably phlebitis, as well as the more recent introduction of penicillinase-resistant semisynthetic penicillins have led to a decline in its use. However, orally administered vancomycin may be the drug of choice in one form of severe staphylococcal disease, enterocolitis. The following cases illustrate its use in this situation.Case ReportsW.E. (K.C.H. 427367), a 69-year-old man with Laennec's cirrhosis, had fever and diarrhea while receiving neomycin by mouth for the . . .
749-4 Role of Autonomic Tone in the Induction of Coronary Spasm in Patients with Variant Angina with or without Obstructive Coronary Stenoses
Authors: Gaetano A. Lanza, Patrizia Pedrotti, Elena Bia, Vincenzo Pascen, Michele Lucenle, Filippo Crea, Attilio Maseri
Journal: Journal of the American College of Cardiology (1995)
An unusual cause of abdominal fullness in a patient with Raynaud's phenomenon
Authors: A Hokama, K Kishimoto, M Nakamoto, N Kinjo, F Kinjo, J Fujita
Journal: Gut (2008)

A 38-year-old woman presented with abdominal fullness of 3 month’s duration. She denied abdominal pain, diarrhoea and weight loss. She had a 20 year history of Raynaud’s …
Effect of different doses of chlorthalidone on blood pressure, serum potassium, and serum urate.
Authors: C Bengtsson, G Johnsson, R Sannerstedt, L Werko
Journal: BMJ (1975)

Chlorthalidone given to 40 hypertensive women significantly decreased blood pressure and serum potassium levels and increased the serum urate concentration. There were no individual correlations between the reduction in blood pressure and the decrease in serum potassium or the increase in serum urate. A reduction in dosage from 50 mg daily to 50 mg three times a week produced no significant changes in the diastolic or mean blood pressures though the systolic blood pressure was moderately increased. Concomitantly, serum potassium increased and serum urate decreased significantly on the lower chlorthalidone dose. We conclude that high doses of oral diuretics compared with lower ones are of limited further benefit and may increase the risk of clinically significant hypokalaemia and hyperuricaemia.
Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non-Small-Cell Lung Cancer
Authors: F. Cappuzzo, E. Magrini, G. L. Ceresoli, S. Bartolini, E. Rossi, V. Ludovini, V. Gregorc, C. Ligorio, A. Cancellieri, S. Damiani, A. Spreafico, C. T. Paties, L. Lombardo, C. Calandri, G. Bellezza, M. Tonato, L. Crino
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Gefitinib, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has activity against approximately 10% of unselected non–small-cell lung cancer (NSCLC) patients. Phosphatidylinositol 3′-kinase (PI3K)/Akt and Ras/Raf/mitogen-activated protein kinase (MAPK), the two main EGFR-signaling pathways, mediate EGFR effects on proliferation and survival. Because activation of these pathways is dependent on the phosphorylation status of the components, we evaluated the association between phosphorylation status of Akt (P-Akt) and MAPK (P-MAPK) and gefitinib activity in patients with advanced NSCLC. Methods: Consecutive patients (n = 106) with NSCLC who had progressed or relapsed on standard therapy received gefitinib (250 mg/day) until disease progression, unacceptable toxicity, or patient refusal. P-Akt and P-MAPK positivity was determined with immunohistochemistry using tumor tissues obtained before any anticancer treatment. Association of P-Akt and time to progression was determined by univariable and multivariable analyses. All statistical tests were two-sided. Results: Of the 103 evaluable patients, 51 (49.5%) had tumors that were positive for P-Akt, and 23 (22.3%) had tumors that were positive for P-MAPK. P-Akt–positivity status was statistically significantly associated with being female ( P <.001), with never-smoking history ( P = .004), and with bronchioloalveolar carcinoma histology ( P = . 034). Compared with patients whose tumors were negative for P-Akt, patients whose tumors were positive for P-Akt had a better response rate (26.1% versus 3.9%; P = .003), disease control rate (60.9% versus 23.5%; P <.001), and time to progression (5.5 versus 2.8 months; P = .004). Response rate, disease control rate, and time to progression did not differ according to P-MAPK status. The multivariable analysis showed that P-Akt positivity was associated with a reduced risk of disease progression (hazard ratio = 0.58, 95% confidence interval = 0.35 to 0.94). Conclusions: Patients with P-Akt–positive tumors who received gefitinib had a better response rate, disease control rate, and time to progression than patients with P-Akt–negative tumors, suggesting that gefitinib may be most effective in patients with basal Akt activation.
Serum reactivity to other indoor ficus plants in patients with allergy to weeping fig (<i>Ficus benjamina</i>)
Authors: I. G. K. Axelsson, S. G. O. Johansson, P. H. Larsson, O. Zetterström
Journal: Allergy (1991)

Ornamental plants have long been used for indoor decoration. An example is the india rubber tree ( Ficus elastica ). With the increased popularity of green plants, both in private homes and public premises, small‐leaf species, such as weeping fig or Ficus benjamina (Fb), have become widely used. Exposure to dust from Fb may cause sensitization and allergic airway symptoms, which among occupationally exposed plant keepers occur both in atopics and non‐atopics. The serum reactivity to sap extracts from Fb and seven other indoor plants of the genus Ficus were investigated with RAST and a RAST inhibition technique, using sera from 12 atopic subjects and 12 plant keepers, sensitized to Fb. The allergenic similarity between the different extracts was found to be extensive. The specific IgE antibodies with the highest concentrations in serum were those against Fb and its variegate form, “star light”, with decreasing values for the other species, especially those with larger leaves. The binding of IgE antibodies to the other Ficus RAST discs could be completely inhibited by extract of Fb. These reactions were probably due to cross‐reactivity. Sensitization is believed to occur by inhalation of allergen‐enriched dust, emanating from the leaves of the plants. The high allergenic potency of the species with many small leaves may be due to their large total leaf area.
John Herman Higgins
Authors: I. Abu-Arafeh
Journal: BMJ (2008)

After completing his compulsory national service as a trainee nurse in the Royal Air Force, John Herman Higgins decided to study medicine. He found a day job in a wool merchants and cycled across Manchester to night school to study for university entrance exams. His enthusiasm paid off, and John commenced his medical school education at the University of Edinburgh in 1951, subsequently graduating MBChB in 1957. He undertook his pre-registration …
Maximum Phosphorylation of the Cardiac Ryanodine Receptor at Serine-2809 by Protein Kinase A Produces Unique Modifications to Channel Gating and Conductance Not Observed at Lower Levels of Phosphorylation
Authors: Simon Carter, John Colyer, Rebecca Sitsapesan
Journal: Circulation Research (2006)

It is suggested that protein kinase A (PKA)-dependent phosphorylation of cardiac ryanodine receptors (RyR2) is linked to the development of heart failure and the generation of fatal cardiac arrhythmias. It is also suggested that RyR2 is phosphorylated to 75% of maximum levels in heart failure resulting in leaky, unregulated channels gating in subconductance states. We now demonstrate that this is unlikely, as RyR2 isolated from nonfailing cardiac muscle is phosphorylated to 75% of maximum at serine-2809, and in this situation, RyR2 displays low open probability (P(o)) (0.059+/-0.010 [SEM]; n=30) and normal regulation of gating by Ca(2+) and other ligands. However, when serine-2809 is PKA phosphorylated to maximum levels on RyR2, unique changes in channel behavior are observed. The channel displays enhanced single-channel conductance, very long open states causing large increases in P(o), and no evidence of subconductance states. Dephosphorylation of channels by protein phosphatase 1 (from 75% to near 0% at serine-2809) also enhances RyR2 channel activity through abbreviation of closed lifetimes. We propose that channels phosphorylated to 75% of maximum at serine-2809 occupy a natural low point in the RyR2 activity landscape. This optimizes channel control, which can be accomplished either by enhanced or decreased phosphorylation, making the channel particularly sensitive to the kinase:phosphatase balance. Pathological situations such as heart failure might upset this balance and thereby permit prolonged stoichiometric phosphorylation of serine-2809, which would be required for dysregulation of SR Ca(2+) release.
Abstract 784: Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed
Authors: Susumu Takeuchi, Masahiro Seike, Rintaro Noro, Chie Soeno, Teppei Sugano, Fenfei Zou, Masaru Matsumoto, Akihiko Miyanaga, Yuji Minegishi, Kaoru Kubota, Akihiko Gemma
Journal: Cancer Research (2014)

Abstract Background: Pemetrexed (PEM) is currently recommended as one of the standard anticancer drugs for malignant pleural mesothelioma (MPM). However, the mechanism of the sensitivity of MPM to PEM remains unclear. Materials and Methods: We analyzed the antitumor effects of PEM in six MPM cell lines by MTS assay. To identify genes associated with drug sensitivity, we conducted gene expression profiling on the same set of cell lines using GeneChips and pathway analysis. Results: Three cell lines were sensitive to PEM. Eighteen transcripts and fourteen genes identified by Gene-chips were significantly correlated with sensitivity to PEM. Pathway analysis revealed that osteopontin (SPP1/OPN) was an important target in PEM sensitivity. Overexpression of SPP1/OPN was observed in the sensitive cells by quantitative RT-PCR analysis and Western blotting. Introduction of SPP1/OPN by lentiviral vector significantly enhanced the invasion activities of MPM cells. PEM treatment with SPP1/OPN knockdown inhibited the PEM-induced cell growth-inhibitory effect in PEM-sensitive cells. Expression of SPP1/OPN and AKT phosphorylation significantly decreased after PEM treatment of the PEM sensitive cells. High immunohistochemical expression of SPP1/OPN was observed in two of three MPM patients who had a partial response to PEM-based chemotherapy. Conclusion: PEM has anti-tumor effects in MPM cells dependent on SPP1/OPN overexpression resulting in AKT activation. Our results suggest that SPP1 may be used as a single predictive biomarker of the effectiveness of PEM treatment in MPM. Citation Format: Susumu Takeuchi, Masahiro Seike, Rintaro Noro, Chie Soeno, Teppei Sugano, Fenfei Zou, Masaru Matsumoto, Akihiko Miyanaga, Yuji Minegishi, Kaoru Kubota, Akihiko Gemma. Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 784. doi:10.1158/1538-7445.AM2014-784