tbuckley/cabot-search huggingface dataset:
Defence against bacterial drug resistance.
Authors: L P Garrod
Journal: BMJ (1976)

Everyone knows that acquired microbic resistance is the Achilles heel of chemotherapy.All living things can acquire some resistance to noxious agents-man to morphine, for instance.Bacteria are no exception: they can become more resistant in some degree even to ordinary germicides.But nothing in the whole of nature equals the resistance which can develop to antibiotics; it seems here as if the sharper the weapon the more completely it can be blunted.A 10-fold change can deprive an antibacterial drug of much of its usefulness, but some increases are of the order of 1000-fold or even more.Since this change is a prolific cause of treatment failure it is worth while to inquire how it can be avoided. Origins of resistanceHow does resistance arise in bacteria ?One process is simply selection; treatment with an antibiotic eliminates sensitive strains and enables an originally very small minority of resistant ones to survive and spread.This is undoubtedly what happened among staphylococci in the early days of penicillin.When exposure to a drug-antibiotic or synthetic-is followed by resistance in a previously sensitive strain this is usually attributed to mutation.This is undeniable and has been con- clusively proved in some instances, but when resistance increases slowly over a period ofyears some form of adaptation seems a more likely explanation than a long series of small genetic changes, and this hypothesis had a strong advocate in the late Sir Cyril Hinshelwood.1There are three mechanisms whereby genetic elements determining drug resistance, often multiple, can be transferred from one bacterial cell to another.They are transfor- mation, the uptake of genetic material already liberated from another cell; transduction by bacteriophage, which can occur in many species; and conjugation, which occurs only between Gram-negative bacilli, although of many different genera. Motives for discouraging resistanceThe main reason for devising treatment to which resistance will not develop is to ensure the patient's recovery.But it is well to look further into the consequences of failure, which may
"Double depression": two-year follow-up
Authors: M B Keller, P W Lavori, J Endicott, W Coryell, G L Klerman
Journal: American Journal of Psychiatry (1983)

Of 316 patients with a major depressive disorder who were followed for between 6 months and 2 years, 80 (25%) had a preexisting chronic minor depression of at least 2 years' duration. The chronic minor depression reduced the apparent effect of the known predictors of recovery and relapse from the major depressive disorder and predicted a very pernicious course for the chronic depression. Furthermore, the longer the patient continued to suffer from a chronic minor depression after recovering from the major depression, the greater the probability that relapse into another major depression would preempt recovery from the chronic depression.
Dynamic in vivo biocompatibility of angiogenic peptide amphiphile nanofibers
Authors: Shahram Ghanaati, Matthew J. Webber, Ronald E. Unger, Carina Orth, James F. Hulvat, Sarah E. Kiehna, Mike Barbeck, Angela Rasic, Samuel I. Stupp, C. James Kirkpatrick
Journal: Biomaterials (2009)
Myocardial Infarction or Acute Myopericarditis-Reply
Authors: Peter G. Hanson
Journal: JAMA (1983)

In Reply.—  Drs Karjalainen and Heikkila have emphasized the frequent similarity between acute myopericarditis and myocardial infarction. Our case report of myocardial infarction in a highly conditioned swimmer also considered the possibility of myopericarditis. However, the absence of preceding symptoms of viral illness and the highly localized uptake of technetium Tc 99m pyrophosphate in the anterolateral wall argued against myopericarditis. We did not perform viral serological studies because a primary viral isolate was not recovered from the throat.  A limited number of radionuclide studies in documented viral myopericarditis have shown predominantly diffuse uptake patterns 1 with a single report of localized radionuclide uptake. 2 Each of these cases had definite preceding symptoms of viral illness.  We agree that myopericarditis may mimick acute myocardial infarction. We also emphasize that myocardial infarction is well documented in young adults with normal coronary arteries. 3 In some of these cases, exercise is a precipitating
The Methylcytosine Dioxygenase Tet2 Promotes DNA Demethylation and Activation of Cytokine Gene Expression in T Cells
Authors: Kenji Ichiyama, Tingting Chen, Xiaohu Wang, Xiaowei Yan, Byung-Seok Kim, Shinya Tanaka, Delphine Ndiaye-Lobry, Yuhua Deng, Yanli Zou, Pan Zheng, Qiang Tian, Iannis Aifantis, Lai Wei, Chen Dong
Journal: Immunity (2015)
Critical windows of exposure to household pesticides and risk of childhood leukemia.
Authors: Xiaomei Ma, Patricia A Buffler, Robert B Gunier, Gary Dahl, Martyn T Smith, Kyndaron Reinier, Peggy Reynolds
Journal: Environmental Health Perspectives (2002)

The potential etiologic role of household pesticide exposures was examined in the Northern California Childhood Leukemia Study. A total of 162 patients (0-14 years old) with newly diagnosed leukemia were rapidly ascertained during 1995-1999, and 162 matched control subjects were randomly selected from the birth registry. The use of professional pest control services at any time from 1 year before birth to 3 years after was associated with a significantly increased risk of childhood leukemia [odds ratio (OR) = 2.8; 95% confidence interval (CI), 1.4-5.7], and the exposure during year 2 was associated with the highest risk (OR = 3.6; 95% CI, 1.6-8.3). The ORs for exposure to insecticides during the 3 months before pregnancy, pregnancy, and years 1, 2, and 3 were 1.8 (95% CI, 1.1-3.1), 2.1 (95% CI, 1.3-3.5), 1.7 (95% CI, 1.0-2.9), 1.6 (95% CI, 1.0-2.7), and 1.2 (95% CI, 0.7-2.1), respectively. Insecticide exposures early in life appear to be more significant than later exposures, and the highest risk was observed for exposure during pregnancy. Additionally, more frequent exposure to insecticides was associated with a higher risk. In contrast to insecticides, the association between herbicides and leukemia was weak and nonsignificant. Pesticides were also grouped based on where they were applied. Exposure to indoor pesticides was associated with an increased risk, whereas no significant association was observed for exposure to outdoor pesticides. The findings suggest that exposure to household pesticides is associated with an elevated risk of childhood leukemia and further indicate the importance of the timing and location of exposure.
Diabetic Acidosis During Chlorothiazide Therapy
Authors: Samuel J. N. Sugar
Journal: JAMA (1961)

CHLOROTHIAZIDE is widely used in the treatment of pregnant patients with edema.<sup>1</sup>When this condition is complicated by diabetes, the increased excretion of sodium, potassium, and chlorides due to this drug may accelerate ketosis. Two cases of diabetes with pregnancy in whom acidosis may have been aggravated by administration of chlorothiazide are here described. <h3>Case Reports</h3><h3>Case 1.—</h3> A 38-year-old housewife was admitted to Providence Hospital, Washington, D. C., on Oct. 30, 1959, complaining of low abdominal pains. She had been a diabetic for 21 years and at the time of admission was 7 months pregnant. Expected confinement date was Dec. 22, 1959. At 3 months gestation her diabetes was well controlled by 10 units of isophane (NPH) insulin a day. She then noted persistent glycosuria and gradually increased the insulin dose to 40 units of isophane at 6 A. M., supplemented by 10 to 20 units of regular
Preventive medicine and public health
Authors: William L. Fleming
Journal: JAMA (1963)

This is the third edition of a distinctive text which has been one of the leaders in its field since it was first published in 1946. The first edition was noteworthy for the breadth of viewpoint of its experienced author (Smillie); for its graceful dedication to Lemuel Shattuck, the remarkably public-healthminded Bostonion book seller of a century ago whose apt statements were liberally quoted; for its thorough coverage of the field; and for the usefulness of its frequently quoted definitions of "preventive medicine" and "public health." The second edition, in 1952, changed the format little in bringing the book up-to-date, but the present edition has been more extensively revised in format, as well as in content, while retaining much of the flavor of the original. Kilbourne has revised extensively the coverage of infectious diseases which are classified in a particularly useful epidemiologic fashion. Bross has revised the material on biostatistics.
An ELISA Technique for Quantification of Surfactant Apoprotein (SP)-C in Bronchoalveolar Lavage Fluid
Authors: REINHOLD SCHMIDT, WOLFRAM STEINHILBER, CLEMENS RUPPERT, CHRISTINA DAUM, FRIEDRICH GRIMMINGER, WERNER SEEGER, ANDREAS GÜNTHER
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Pulmonary surfactant apoprotein C (SP-C) is a small, unique peptide that contributes to the reduction of alveolar surface tension. Due to the extreme hydrophobic nature of this peptide it was hitherto not possible to quantify SP-C in biological samples by immunological techniques. Using a newly developed polyclonal antibody raised against recombinant human SP-C in rabbits, we now describe an enzyme-linked immunosorbent assay (ELISA) to quantitate SP-C in bronchoalveolar lavage fluid (BALF). Solid phase binding of the hydrophobic SP-C was achieved by transfer of the standard or BALF samples (diluted in 80% isopropanol, pH 3.5) to polystyrene microtiter plates. Sequential treatment with trifluoroethanol and methanol (2 × ) was employed to improve antigen presentation and to minimize the influence of phospholipids. With this assay, SP-C from human, rabbit, porcine, and bovine surfactant was detectable. No cross-reactivity of the antibody to human SP-A and monomeric and dimeric SP-B was encountered. Total serum proteins did not affect ELISA signals, as evident from spiking experiments. The detection limit of the ELISA ranged below 3 ng/ml, and intra- and interassay coefficients of variation were 3.5% (n = 16) and 5.3% (n = 6), respectively. Serial dilutions of BALF showed good linearity, and excellent recovery rates were obtained upon spiking of human BALF. A mean value of 579.5 ± 45.9 ng/ml (mean ± SEM) SP-C was found in BALF samples of human healthy volunteers (n = 22), corresponding to 26.61 ± 1.91 μ g SP-C/mg total phospholipids (PL). SP-C levels were significantly lower in BALF of patients with acute respiratory distress syndrome (ARDS) (286.9 ± 19.8 ng/ml [p < 0.001]; 13.92 ± 1.93 μ g SP-C/mg PL [p < 0.001], n = 48). We conclude that SP-C may be quantified with high specifity, reproducibility, and sensitivity in bronchoalveolar lavage samples by the presently described ELISA technique and that SP-C levels are significantly decreased in ARDS.
HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors
Authors: S Pillozzi, MF Brizzi, M Balzi, O Crociani, A Cherubini, L Guasti, B Bartolozzi, A Becchetti, E Wanke, PA Bernabei, M Olivotto, L Pegoraro, A Arcangeli
Journal: Leukemia (2002)
Is Accelerated Partial Breast Irradiation Appropriate Adjuvant Therapy for Patients with Ductal Carcinoma In-Situ?
Authors: E. Careaga, J. Hughes, L. Allen, R. Carella, T. Frazier
Journal: Cancer Research (2009)

Abstract Introduction: Accelerated partial breast irradiation (APBI) using high-dose rate (HDR) balloon catheter breast brachytherapy following wide segmental resection of the breast has been shown to be equivalent to whole breast irradiation (WB-XRT) in the treatment of stage-I breast carcinoma. Because the majority of all breast cancers recur in the same quadrant as the original tumor, the advantages of this treatment compared with WB-XRT include concentration of radiation in the area where cancer is most likely to recur, shorter treatment duration, and greater patient acceptance. This study examined the rate of local/regional recurrence in patients diagnosed with stage-0 breast cancer, specifically ductal carcinoma in-situ (DCIS), following wide segmental resection of the breast and treatment with APBI using HDR balloon catheter breast brachytherapy.Methods: An IRB-approved, single-institution, retrospective chart review was conducted identifying 40 patients diagnosed with stage-0 breast cancer between March, 2004 and April, 2008 who were treated with wide segmental resection of the breast followed by APBI using HDR MammoSite™ balloon catheter breast brachytherapy. Outcome measures included rates of same-quadrant recurrence, ipsilateral second-primary occurrence, and regional recurrence.Results: Patient age ranged from 44 to 89 years (median = 69 years) with a median follow-up of 40 months (range: 16 to 60 months). All 40 patients had DCIS. One patient of 40 (2.5%) had DCIS with an additional focus of lobular carcinoma in-situ. 29 of 40 patients (72.5%) were estrogen receptor (ER) positive. Of these 29 patients, 17 were also progesterone receptor (PR) positive. One patient (2.5%) at 38 months experienced a local recurrence of DCIS with micro-invasion and a synchronous focus of invasive ductal carcinoma in a separate quadrant. This was subsequently treated with total mastectomy, sentinel lymph node mapping, and axillary lymph node dissection. No other patients experienced local-regional recurrence or ipsilateral primary breast cancer occurrence.Conclusion: Patients with DCIS can be effectively treated with APBI/HDR balloon catheter breast brachytherapy following wide segmental breast resection. The rate of local-regional recurrence was 2.5% at a median follow-up time of 40 months. This is consistent with that of patients with DCIS treated with wide segmental breast resection followed by WB-XRT. Long-term follow-up will be required to assure these rates remain favorable. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2116.
A role for ring-closing metathesis in medicinal chemistry: Mimicking secondary architectures in bioactive peptides
Authors: María Jesús Pérez de Vega, María Isabel García-Aranda, Rosario González-Muñiz
Journal: Medicinal Research Reviews (2010)

Synthetically versatile and easy to carry out, Ring-Closing Metathesis (RCM) constitutes an attractive chemical tool, easily amenable for multiple substrates in mild conditions. In medicinal chemistry, the use of RCM has been especially prolific during the last few years. An important application that has benefited from this reaction is the stabilization of spatial conformations in bioactive peptides, since their 3D arrangements play relevant roles in biomolecular recognition processes. RCM reaction is being widely used to introduce conformational constraints into small peptides, through the generation of cyclic structures from appropriate linear precursors. As an alternative to strategies like disulfide or lactam-bridged cyclizations, RCM shows the additional advantage of generating hydrocarbon bridges, less prone to metabolic degradation, and metabolically more stable, which could benefit their pharmacokinetic properties. Particularly remarkable is the application of RCM to the preparation of small peptide modulators able to mimic epitopes identified as hotspots within the surface contact areas in protein-protein interactions (PPIs). This review deals with the replacement of S-S and thioether linkages of cyclic peptides by C-C-bridges and with the stabilization of peptide secondary architectures (α-helix, β-hairpins, β-turns) through RCM, as a useful strategy for the modulation of therapeutically relevant signaling pathways.
The treatment of combination chemotherapy‐resistant Hodgkin disease with single‐agent vinblastine
Authors: Robert D. Warren, Richard A. Bender, Larry Norton, Robert C. Young
Journal: American Journal of Hematology (1978)

Abstract Vinblastine has been an effective single agent for initial induction therapy of advanced Hodgkin disease. To investigate the efficacy of this drug in combination chemotherapy‐resistant Hodgkin disease, 29 patients with Stage III or Stage IV disease who had previously received MOPP (nitrogen mustard, vincristine, prednisone, procarbazine) or C‐MOPP (cyclophosphamide, vincristine, prednisone, procarbazine) for initial remission induction were treated with vinblastine at the time of relapse, either as the first single agent at relapse (n = 17) or following unsuccessful attempts at reinduction with combination chemotherapy (n = 9) or other single agents (n = 3). Eighteen patients (62%) achieved an objective regression of disease. Two patients (7%) had a complete remission of nine and ten months duration and 16 patients (55%) had a partial remission with a median duration of four months. A response to combination chemotherapy did not predict for a vinblastine response, nor did nodal versus visceral involvement at time of relapse or initial stage of Hodgkin disease. There were no significant differences in age, sex, vinblastine dose, or disease duration between those patients who responded to vinblastine and those who did not. Patients with nodular sclerosis histology responded better to subsequent vinblastine therapy. Hematologic toxicity was moderate with 17 patients developing leukopenia (&lt; 3,000 cells/mm 3 ) and 12 patients developing thrombocytopenia (&lt; 100,000 cells/mm 3 ). The overall response rate of vinblastine in combination chemotherapy‐resistant Hodgkin disease is comparable to vinblastine single‐agent therapy for initial induction and appears not to be cross‐resistant with combinations containing vincristine.
Crystal Structure of Vδ1 T Cell Receptor in Complex with CD1d-Sulfatide Shows MHC-like Recognition of a Self-Lipid by Human γδ T Cells
Authors: Adrienne M. Luoma, Caitlin D. Castro, Toufic Mayassi, Leslie A. Bembinster, Li Bai, Damien Picard, Brian Anderson, Louise Scharf, Jennifer E. Kung, Leah V. Sibener, Paul B. Savage, Bana Jabri, Albert Bendelac, Erin J. Adams
Journal: Immunity (2013)
A Case of Puerperal Eclampsia (Ante Laborem) With Recovery.
Authors: E. Viko
Journal: JAMA (1898)

Park City, Utah, Jan. 8, 1898. <h3>To the Editor:</h3> —As there is a good deal of uncertainty in regard to the exact pathology and treatment of puerperal eclampsia, it would possibly throw more light on the management of this dreaded disease if the physicians reported every case in their practice and the line of treatment pursued; especially does this seem important when it is remembered that according to statistics the mortality is 40.5 per cent, if the convulsions set in before the time of labor and about 29 per cent. during labor. Oct. 28, 1897, I was called on to prescribe for Mrs. S., age 22; pregnant about thirty-seven to thirty-eight weeks; primipara. She was troubled some with vomiting and complained of being very nervous and restless so that she could sleep but very little during the night; had quite a severe pain in the stomach and a good deal
Identification of K-ras Mutations in Pancreatic Juice in the Early Diagnosis of Pancreatic Cancer
Authors: Philippe Berthelemy
Journal: Annals of Internal Medicine (1995)

Objective: To develop an early diagnostic test for pancreatic cancer based on the identification of K-ras mutations in pure pancreatic juice collected during endoscopic retrograde pancreatography. Design: Prospective study with masked comparison. The standard criteria for the diagnosis of pancreatic cancer were pancreatography or surgery (or both) and histopathology, with follow-up ranging from 6 to 40 months. Setting: Referral center. Patients: 24 patients with no pancreatic disease (group 1); 29 patients with nontumoral pancreatic disease (group 2); and 22 patients with pancreatic tumor (group 3). Endoscopic ductal aspiration of cells or brush cytology was done on patients having endoscopic retrograde pancreatography for diagnostic or therapeutic reasons. Main Outcome Measure: Confirmation of mutation rates in patients with pancreatic cancer. Results: K-ras gene analysis was done by polymerase chain reaction-mediated restriction fragment length polymorphism analysis and direct sequencing. All patients from groups 1 and 2 (n = 53) had a normal sequence for the K-ras 12th codon (group 1, 0% [95% CI, 0% to 14%]; group 2, 0% [CI, 0% to 12%]). Mutations were seen in 17 of the 22 patients in group 3 (77% [CI, 55% to 92%]). Two of the 17 had no evidence of pancreatic cancer when K-ras was first studied. One had chronic abdominal pain and the other presented with acute pancreatitis. Both were initially free of any pancreatic mass, but they developed tumors 18 and 40 months, respectively, after the K-ras mutations were identified. Conclusion: Identification of K-ras mutations in samples of pancreatic juice may be useful in differentiating between pancreatic cancer and noncancerous pancreatic diseases. K-ras mutation can precede clinical evidence of pancreatic cancer, but the clinical implications of this finding need further study.
Notes on Paganini
Authors: J. W. Miller
Journal: JAMA (1967)

<h3>To the Editor:—</h3> The article on Paganini by Drs. Richard D. Smith and John W. Worthington (<b>199</b>: 820, 1967) is an excellent contribution not only to the reputation of the great violinist but to medicine. That such a cadaverous, freakish, harassed individual turned out to be one of the world's greatest violinists is miraculous indeed. One item, which needs more light, is debatable. In the secord paragraph the authors state: "He was a talented composer also; but we are less familiar with his compositions because they are seldom performed, owing partly to the extraordinary difficulties imposed upon the artist." I am the proud possessor of three recordings of his violin concertos played flawlessly and beautifully by Menuhin. The finale of the second violin concerto in B minor, the rondo, is as enchantingly beautiful as it is difficult. Paganini's contemporary, the great pianist Franz Liszt, was so fascinated by the scintillating
Nicotinamide preferentially protects glycolysis in dermal fibroblasts under oxidative stress conditions
Authors: H.A. Rovito, J.E. Oblong
Journal: British Journal of Dermatology (2013)

Daily exposure of human skin to environmental insults such as solar radiation, pollution and smoke can lead to an elevation of oxidative stress, causing premature acceleration of skin ageing. Oxidative stress is known to disrupt cellular metabolism, which negatively impacts the skin's functionality at the cellular and tissue level.To examine the changes in cellular metabolism due to oxidative stress.Glycolysis and oxidative phosphorylation rates in human dermal fibroblasts were monitored in real time under controlled nonlethal oxidative stress conditions. Hydrogen peroxide was utilized as a surrogate stressor because numerous environmental stressors as well as intrinsic ageing trigger its production.Hydrogen peroxide ranging between 0.5 and 3 mmol L(-1) caused a significant decrease in glycolytic and oxidative phosphorylation rates along with cellular ATP levels. Nicotinamide (NAM) was found to protect dose dependently as well as restore glycolytic rates concurrent with restoring ATP to control levels. NAM had an effective dose-response range between 0.1 and 1.0 mmol L(-1) , with maximal effects attained at 0.5 mmol L(-1) . Relative to oxidative phosphorylation, NAM was able to provide a diminished level of protection. FK866, a known NAM phosphoribosyltransferase inhibitor, was found to inhibit the protective effects of NAM significantly, suggesting part of the NAM mechanism of action involves nicotinamide adenine dinucleotide (NAD(+) ) synthesis.These results support previous findings that NAM protects cellular metabolism from oxidative stress by preferentially affecting glycolysis. Additionally, part of its mechanism of action appears to include NAD(+) synthesis.