tbuckley/cabot-search huggingface dataset:
Prescribing Aconite by the Old Pharmacopeia.
Authors: L. Buckle
Journal: JAMA (1906)

New York, Dec. 22, 1906. <h3>To the Editor:</h3> —On looking over a few of the latest prescription files at several drug stores, I was surprised to find that many physicians still prescribe tincture of aconite in the old doses. Most druggists by this time have the new official tincture of 10 per cent, strength; and of this they dispense the quantity as prescribed. The result must, of necessity, be disappointing to both physician and patient, since a tincture of 10 per cent, can not have the same therapeutic effect, in the same doses, as a tincture of 35 per cent. Some physicians not only did not know that the strength of this tincture had been reduced, but were entirely innocent of the existence of the new Pharmacopeia. One physician who happened to prescribe tincture of aconite in five minim doses, in my presence, thought he was heroic in his doses.
Regressing atypical histiocytosis and lymphomatoid papulosis: variants of the same disorder?
Authors: R. CERIO, M.M. BLACK
Journal: British Journal of Dermatology (2006)

We report a patient with lymphomatoid papulosis who developed a lesion with the clinicopathological features of regressing atypical histiocytosis. Immunohistochemical studies supported a T-cell histogenesis and many of the atypical cells demonstrated BerH2 (Ki-I antigen) positivity. The case supports the view that regressing atypical histiocytosis and lymphomatoid papulosis are different manifestations of the same disease spectrum.
Continuing Medical Education at a Crossroads
Authors: Dennis K. Wentz
Journal: JAMA (1990)

No one should be surprised by the report by Stross and DeKornfeld<sup>1</sup>in this issue ofThe Journalthat Michigan physicians demonstrated a remarkable level of compliance with a state regulation that mandates continuing medical eduction (CME) for reregistration of license. (Among 29 states with such a requirement, it is operational in 22.) Only five practitioners of 967 randomly audited to determine their compliance had less than the minimum number of 75 category I (category I definition of the Michigan Board of Medicine) hours per 3 years, and the average physician reported 175 hours of category I activities over 3 years. This is a "good news" type of story that the public too rarely hears about physicians in our country; no profession I am aware of takes its continuing education quite as seriously. The authors' conclusion is not surprising. They state: "Because of problems with documentation, only category I—
Comparative study of the biomechanical performance of trained and untrained skeletal muscle
Authors: M PETROU, C BOWLES, M YACOUB
Journal: Cardiovascular Research (1997)

Changes in contraction and relaxation parameters during chronic electrical stimulation can exert profound effects on diastolic augmentation during skeletal muscle assistance (SMA) of the circulation, in both short and long term. The physiological properties of latissimus dorsi muscle (LD) performance in a system that mimics the clinical setting has not been adequately studied. Objective: To quantify changes in the biomechanical performance of trained and untrained skeletal muscle in relation to circulatory assistance using an ex-vivo Windkessel mock circulation. Methods: Twelve Welsh Mountain sheep were divided into 2 groups: Group A ( n = 6) underwent implantation of intramuscular electrodes into the left LD connected to a myostimulator (Telectronics Pacing Systems, Inc., Colorado) and progressively trained by burst stimulation over a 12-week period using standard stimulation parameters (2.5-5 V, 35 Hz, 6 pulses per burst, 240 μs per pulse); Group B ( n = 6) were the untrained controls. At the end of 12 weeks, the LD was mobilised on its neurovascular pedicle and wrapped around a latex rubber aorta connected to two Windkessel chambers pressurised to 70 mmHg and stimulated to contract 40 times per minute continuously for 60 min. Pressure change per contraction (augmentation, ΔP), volume displacement, contraction (C t ) and relaxation to 90% (R t90 ) times, and the standardised rate of change of pressure generation (+dP/dt:ΔP) and decay (−dP/dt:ΔP) were determined and assessed for potential clinical efficacy. Results: In Group A, the LD was fatigue-resistant in all 6 animals with a mean pressure augmentation of 13.7 (s.e.m. 1.3) mmHg and mean stroke volume of 12.5 (s.e.m. 1.0) ml. These muscles were slow with a mean C t and +dP/dt:Δmax of 243.2 (s.e.m. 6.1) ms and +6.5 s −1 , respectively, and R t90 and −dP/dt:Δmax of 261.0 (s.e.m. 4.8) ms and −7.8 s −1 , respectively. In contrast, the LD in Group B was fatiguable with a mean pressure augmentation and stroke volume of 24.6 (s.e.m. 0.9) mmHg and 21.1 (s.e.m. 0.7) ml at 1 min and only 5.4 (s.e.m. 0.3) mmHg and 5.2 (s.e.m. 0.3) ml, respectively, at 30 min ( P < 0.001). These muscles were faster at all time points compared to group A ( P < 0.02). Acute diminution of power output per contraction in Group B coincided with a prolongation in the R t90 by 101% compared to the C t which decreased by less than 5% ( P < 0.001). The C t /R t90 ratio did not significantly change during performance testing in Group A (fatigue-resistant animals) ( P > 0.1). Conclusion: Using a mock circulation system, we have identified significant differences in biomechanical properties of trained and untrained skeletal muscle. Optimisation of these parameters during and after electrical training may alter the clinical efficacy of SMA.
Kupffer cells required for high affinity peptide-induced deletion, not retention, of activated CD8+ T cells by mouse liver
Authors: Yuhshi Kuniyasu, Suhail Mohammed Marfani, Irteza Bin Inayat, Shehzad Zafar Sheikh, Wajahat Zafar Mehal
Journal: Hepatology (2004)

The immune response to foreign antigens in the liver is often suboptimal and this is clinically relevant in chronic persistence of hepatotropic viruses. In chronic infection with the hepatitis C virus, activated CD8+ T cells specific for viral epitopes are present in the peripheral blood and the liver, yet viral clearance is unusual. To define the fate of activated CD8+ entering the liver, we developed a mouse model of portal vein injection of activated CD8+ T cells in vivo. Activated CD8+ T cells are retained very efficiently by the liver and undergo an approximately 8-fold expansion in the first 48 hours. This expansion is followed by apoptosis and a decline in numbers of the retained cells over the next 4 days. The presence of high affinity (HA) antigen does not affect the initial retention by the liver but greatly limits the expansion in the first 48 hours by increasing apoptosis of the retained cells. In the absence of Kupffer cells, the initial retention and expansion are unchanged, but HA antigen does not limit the expansion of the liver CD8+ T cell pool. In conclusion, these data identify a previously unknown phase of CD8+ T cell expansion after entering the liver, demonstrate that HA antigen limits the hepatic CD8+ T cell pool by inducing apoptosis, and that this effect requires Kupffer cells. Interfering with antigen presentation by Kupffer cells may be a strategy to limit HA antigen-induced deletion of activated CD8+ T cells entering the liver.
Abstract 1043: Distinctive roles of Smad3 C-tail and linker phosphorylation between cancer progression and suppression in TGF-beta1/Smad3 signal
Authors: Eunjin Bae, Akira Ooshima, Seong-Jin Kim
Journal: Cancer Research (2014)

Abstract Transforming growth factor B1 (TGF-B) is the prototype of a large family of pleiotropic polypeptide cytokines that regulate a multitude of physiological functions. The ability of TGF-B1/Smad3 signal to inhibit proliferation of epithelial, neuronal and hematopoietic cells from which most human neoplasms originate suggests a role of TGF-B in tumor suppression. Smad3, a key transcription factor in TGF-B signaling, functions as both a positive and negative regulator in carcinogenesis. TGF-B induces phosphorylation of Smad3 C-terminal SXS motif in its canonical pathway as well as the serine/threonine residues in the linker region. The linker region has been known to contain multiple phosphorylation sites for proline-directed kinases such as CDK, c-Jun, p38 MAPK, Erk and GSK-3B. Here we present that the blockade of Smad3 C-terminal phosphorylation by adenoviral dominant-negative mutant promotes tumorigenesis, but markedly inhibits metastasis to the lung as induced by tail-vein injection and orthotopic transplant of human and mouse breast cancer cell lines. Conversely, mutation of Smad3 linker phosphorylation sites greatly suppresses tumorigenesis, while it enhances metastatic dissemination to the lung. In vitro study revealed that the Smad3 linker region is constitutively phosphorylated in the cancer cells, and that the mutation of Smad3 linker phosphorylation sites enhances the TGF-B1-induced EMT, growth arrest and apoptosis, suggesting that the canonical TGF-B1 signal mediated through C-tail phosphorylation is modulated by negative inputs from the linker phosphorylation. Furthermore, the blockade of linker phosphorylation reduces the stem cell population following suppression of mammosphere formation and downregulation of embryonic transcription factors including Oct4, NANOG and Sox-2, and induces apoptosis by repressing an antiapoptotic protein Bcl-2, suggesting that the Smad3 linker phosphorylation retains function for the maintenance of cancer stemness and survival. These results indicate that oncogenic and cancer-suppressive TGF-B1/Smad3 signals are regulated by the site-specific phosphorylation of Smad3 protein, imparting a new aspect to anti-cancer therapies that target the TGF-B signal pathway. This work was supported by a National Research Foundation grant of Korea (2009-0081756) funded by the Korea government. Citation Format: Eunjin Bae, Akira Ooshima, Seong-Jin Kim. Distinctive roles of Smad3 C-tail and linker phosphorylation between cancer progression and suppression in TGF-beta1/Smad3 signal. [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 1043. doi:10.1158/1538-7445.AM2014-1043
Reactive angioendotheliomatosis or intravascular histiocytosis? An immunohistochemical and ultrastructural study in two cases of intravascular histiocytic cell proliferation
Authors: None RIEGER, None SOYER, None LEBOIT, None METZE, None SLOVAK, None KERL
Journal: British Journal of Dermatology (1999)

Two elderly women with complex medical histories presented with erythematous patches, in one case involving the face and forearms, and in the other both elbows. Punch biopsies from both patients revealed intravascular proliferations of medium‐sized and large cells with luminal occlusion typical of angioendotheliomatosis. Immunostaining did not show either lymphocytic or endothelial cell antigens but was consistent with a histiocytic differentiation of the intravascular cells in both cases, and was further substantiated by ultrastructural examination in one case. One patient received a course of cyclophosphamide therapy over 15 days. Skin lesions faded but did not disappear. The patient died 10 months later from cardiac and renal failure, which was most probably unrelated to the skin lesions. In the other case, lesions diminished but did not entirely resolve with treatment with low doses of oral prednisone. Angioendotheliomatosis can be divided into a malignant variant, which is an angiotropic lymphoma mostly of B‐cell phenotype, and a benign, reactive variant, which is characterized by a proliferation of cells expressing endothelial cell markers. Only one case of angioendotheliomatosis with cells of histiocytic differentiation has been published previously under the name of intravascular histiocytosis. Our cases are very similar to the latter. The question arises as to whether intravascular histiocytic cell proliferation is a neoplastic proliferation of histiocytes or an early stage of classic reactive angioendotheliomatosis representing the residual cells associated with organization of microthrombi, which will be later followed by endothelial cell proliferation.
Pseudomonas maltophilia Bacteremia in Children Undergoing Open Heart Surgery
Authors: Margaret C. Fisher
Journal: JAMA (1981)

Pseudomonas maltophilia was isolated from intraoperative blood cultures in eight of 13 children undergoing open heart surgery during a five-week period. Antibiograms were identical and included resistance to prophylactic antibiotics. The source of the outbreak was traced to contamination of both the calibration device used on the pressure monitoring system and the sensor surface of transducers used in this system. In a mock system, calibration with a contaminated device resulted in recovery of the organism from transducer dome fluid. Dye studies confirmed the integrity of the transducer membrane but demonstrated reflux of dome fluid into the monitoring line fluid. A case-control study revealed no patient- or surgery-related factors predisposing to P maltophilia bacteremia and no excess of morbidity or mortality in patients as a result of bacteremia. The outbreak was confined to patients undergoing open heart surgery and was terminated abruptly by sterilization of transducers and revision of the calibration device.
Postconditioning with a volatile anaesthetic in alveolar epithelial cells in vitro
Authors: T. Yue, B. Roth Z'graggen, S. Blumenthal, S. B. Neff, L. Reyes, C. Booy, M. Steurer, D. R. Spahn, T. A. Neff, E. R. Schmid, B. Beck-Schimmer
Journal: European Respiratory Journal (2007)

Acute lung injury is a common complication in critically ill patients. The present study examined possible immunomodulating effects of the volatile anaesthetic sevoflurane on lipopolysaccharide (LPS)-stimulated alveolar epithelial cells (AEC) in vitro . Sevoflurane was applied after the onset of injury, simulating a “postconditioning” scenario. Rat AEC were stimulated with LPS for 2 h, followed by a 4-h co-exposure to a CO 2 /air mixture with sevoflurane 2.2 volume %; control cells were exposed to the CO 2 /air mixture only. Cytokine-induced neutrophil chemoattractant-1, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, as well as the potential protective mediators inducible nitric oxide synthase (iNOS)2 and heat shock protein (HSP)-32, were analysed. Additionally, functional assays (chemotaxis, adherence and cytotoxicity assay) were performed. A significant reduction of inflammatory mediators in LPS-stimulated, sevoflurane-exposed AEC was found, leading to reduced chemotaxis, neutrophil adherence and neutrophil-induced AEC killing. While iNOS2 was increased in the sevoflurane group, blocking experiments with iNOS2 inhibitor did not affect sevoflurane-induced decrease of inflammatory mediators and AEC killing. Interestingly, sevoflurane treatment also resulted in an enhanced expression of HSP-32. The data presented in the current study provide strong evidence that anaesthetic postconditioning with sevoflurane mediates cytoprotection in the respiratory compartment in an in vitro model of acute lung injury.
Genetics and American Society: A Historical Appraisal
Authors: James C. King
Journal: JAMA (1973)

This book is a history of the interaction between genetics and public policy in the United States—a fascinating story that should be more widely known. When Mendel's principles of heredity were discovered by the scientific world in 1900, they became at once the basis for the development of the science of genetics, but they were also appropriated as a catechism by the eugenics movement. Ludmerer traces the shameful story of the eugenicists' use of distorted Mendelian theory to give scientific color to their propaganda for sterilization laws to rid society of "the unfit" and for the restriction of immigration on a basis of racial discrimination. He shows how the experimental geneticists, at first sympathetic to eugenics and even supportive of it, gradually became skeptical and then hostile as genetic research showed more and more clearly that eugenic dogma was not sound science. By the 1930s the excesses of the eugenicists
Local action of phosphate depletion and insulin-like growth factor 1 on in vitro production of 1,25-dihydroxyvitamin D by cultured mammalian kidney cells.
Authors: L Condamine, C Menaa, F Vrtovsnik, G Friedlander, M Garabédian
Journal: Journal of Clinical Investigation (1994)

The hormonal form of vitamin D, 1,25(OH)2D, is synthesized mostly in proximal renal tubular cells. Experimental and clinical studies suggest that the growth hormone may be involved in growth-related fluctuations of plasma 1,25(OH)2D and in the increase of 1,25(OH)2D induced by in vivo phosphate deprivation, an action possibly mediated by insulin-like growth factor 1 (IGF 1). We tested the effects of phosphate depletion and IGF 1 addition on 1,25(OH)2D3 production in cultured kidney cells: opossum kidney (OK) cells, LLC-PK 1, and rabbit's proximal tubular cells. Confluent cell monolayers were preincubated in various phosphate concentrations, in the presence and absence of IGF 1. Then, 5 nM of [3H]25 (OH)D3 or 2 microM of 25 (OH)D3 were added to the medium and the cells were incubated for a further 120 min. The amount of biosynthesized 1,25(OH)2D3 in lipid extracts was determined after two different straight phase high performance liquid chromatographies. The experiment showed the following: (a) LLC-PK 1 and rabbit's cells expressed a detectable ability to synthesize 1,25(OH)2D3, while OK cells did not. (b) Partial or total phosphate deprivation increased the amount of 1,25(OH)2D3 produced, respectively in LLC-PK 1 and in rabbit's cells. (c) IGF 1 (25 ng/ml) increased 1,25(OH)2D3 production in rabbit's cells, particularly in phosphate-free medium (1.6-fold), and in LLC-PK 1 cells, in partial phosphate depletion (2.75-fold in 1 mM phosphate, P = 0.015, n = 5, and 3.2-fold in 0.5 mM phosphate, P = 0.043, n = 4). Our findings demonstrate a local action of phosphate depletion and of IGF 1 on 1,25-dihydroxyvitamin D3 production.
Large-scale Use of Sabin Type 2 Attenuated Poliovirus Vaccine in Singapore During a Type 1 Poliomyelitis Epidemic
Authors: J. H. Hale, M. Doraisingham, K. Kanagaratnam, K. W. Leong, E. S. Monteiro
Journal: BMJ (1959)

In the latter half of 1958 Singapore experienced an epidemic outbreak of poliomyelitis due to the type I virus.Eleven weeks after the first case was reported the Minister of Health in the Singapore Government decided, after consultation, to make available the attenuated type 2 vaccine elaborated by Sabin (1957a, 1957b) for children between the ages of 3 months and 10 years.Dr. Sabin agreed to the release of this vaccine on condition that adequate laboratory control could be assured.The following communication gives the reasons for the selection of the type 2 vaccine, the experimental details, and the results of the campaign.TABLE I.-Incidence of Poliomyelitis in Singapore Since 1946 up to Period of Epidemic
THE USE OF COURT PROBATION IN THE MANAGEMENT OF THE ALCOHOL ADDICT
Authors: KEITH S. DITMAN, GEORGE C. CRAWFORD
Journal: American Journal of Psychiatry (1966)

A pilot and controlled study of a court program using suspended sentence and summary probation to community treatment facilities has been outlined. Preliminary results indicate a dramatic drop in drunk arrest rates. Further studies are contemplated to explain why the decline occurred and to see if there are any characteristics of chronic drunk offenders that would suggest one treatment program rather than another.
Recurrent Aphthous Stomatitis
Authors: David H. Frankel
Journal: JAMA (1985)

To the Editor.—  Recently the clinical dilemma of recurrent aphthous stomatitis was discussed in the QUESTIONS AND ANSWERS section ofThe Journal. 1 The case presented involved a 50-year-old woman with recurrent aphthous stomatitis who had a history of functional bowel  and whose oral symptoms correlated well with the severity of her bowel symptoms. Having recently reviewed the literature on oral Crohn's disease (CD), I am struck by the similarity between this case, the two cases we have reported, and numerous cases reported previously. 2   The label of functional bowel disease, especially in light of oral symptoms, must be fully justified. We do not know, for example, the results of this patient's barium and/or endoscopic studies or whether an oral biopsy was ever performed. Such investigations may be crucial in the case of this woman since it is well reported that patients with CD may present with oral complaints
First Case of AIDS in Hong Kong
Authors: Andrew Y. T. Chan
Journal: JAMA (1985)

To the Editor.—  We wish to update a statement in the authoritative article entitled The Acquired Immunodeficiency Syndrome that appeared in the Oct 19, 1984, issue ofThe Journal.1In the paragraph on etiology, it was stated that  had not been reported in nonhemophiliac, nonaddicted heterosexual Asians.  In February 1985, through the spokesman of the Medical and Health Department, we announced the first confirmed case of AIDS in Hong Kong, which happened also to be the second case in the Far East, the first occurring in a Japanese carrier of ATLV (a type C retrovirus).2  Report of a Case.—  A 46-year-old Chinese man presented in September 1984 with a four-week history of progressive lethargy, fever, and epigastric pain, associated with a 9-kg weight loss. He worked in a restaurant in New York and came back to Hong Kong four months prior to seeking medical advice.  He steadfastly
Potassium Supplements for Hypertension
Authors: Norman M Kaplan, C. V S Ram
Journal: New England Journal of Medicine (1990)

In the continuing search for better and safer ways to control hypertension, various nondrug therapies are widely advocated, and potassium supplements are often listed in the "nondrug prescription." 1 Grimm et al.,2 reporting in this issue of the Journal, examined the antihypertensive effect of a large daily supplement of oral potassium chloride (96 mmol) taken for two years by 142 hypertensive patients (another 145 were given placebo). They found the supplement to be of no benefit.Before addressing the wider issues raised by this paper, a few important points about the design of the study should be noted. First, the . . .
Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels
Authors: Z. Moldoveanu, R.J. Wyatt, J.Y. Lee, M. Tomana, B.A. Julian, J. Mestecky, W.-Q. Huang, S.R. Anreddy, S. Hall, M.C. Hastings, K.K. Lau, W.J. Cook, J. Novak
Journal: Kidney International (2007)