tbuckley/cabot-search huggingface dataset:
Abstract 1345: Role of AMP-activated protein kinase in crosstalk between apoptosis and autophagy in human colon cancer
Authors: Xinxin Song, Seog-Young Kim, Lin Zhang, Yong J. Lee
Journal: Cancer Research (2014)

Abstract Unresectable colorectal liver metastases remain major unsolved issues and more effective regimens are urgently needed. During screening synergistic drug combinations for colon cancer therapy, we identified a novel multimodality treatment for colon cancer cells-chemotherapeutic agent melphalan in combination with proteasome inhibitor bortezomib and mTOR (mammalian target of rapamycin) inhibitor rapamycin. We showed in this study that melphalan triggered apoptosis, bortezomib induced both apoptosis and autophagy, rapamycin caused autophagy, and the combinatorial treatment induced synergistic apoptosis which was mediated through an increase in caspase activation. We observed that mitochondrial dysfunction induced by the combination was linked with altered cellular metabolism and induced AMP-activated protein kinase (AMPK) activation, and thus resulted in Beclin-1 phosphorylated at Ser 93/96. Interestingly, Beclin-1 phosphorylated at Ser 93/96 is sufficient to induce Beclin-1 cleavage by caspase 8 for switching off autophagy to achieve the synergistic induction of apoptosis. The multimodality treatment-induced Beclin-1 cleavage was abolished in Beclin-1 double mutant (D133A/D149A) knock-in HCT116 cells, restoring the autophagy-promoting function of Beclin-1 and suppressing the apoptosis induced by the combination therapy. These observations provide a novel mechanism for AMPK induced apoptosis through interplay between autophagy and apoptosis. Citation Format: Xinxin Song, Seog-Young Kim, Lin Zhang, Yong J. Lee. Role of AMP-activated protein kinase in crosstalk between apoptosis and autophagy in human colon cancer. [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 1345. doi:10.1158/1538-7445.AM2014-1345
Still's Disease in a 70-Year-Old Woman
Authors: Lee Ann Steffe, Charles L. Cooke
Journal: JAMA (1983)

IN 1971, Bywaters<sup>1</sup>reported adultonset Still's disease in 14 patients older than 16 years. The usual clinical picture is that of a young adult with high spiking fever, malaise, a maculopapular rash, and any of numerous associated findings. Laboratory abnormalities are nonspecific. Systemic manifestations often precede the development of arthritis by years, making this a diagnosis to be considered when evaluating fever of undetermined origin. <h3>Report of a Case</h3> A 70-year-old woman was referred to the Medical College of Virginia, Richmond, in June 1980 for further evaluation of an episodic fever of undetermined origin. The fever had been present for two years and had led to five hospital admissions. The patient had previously been treated for right-calf thrombophlebitis, daily fevers, and dry, hacking cough. In October 1978, severe anterior pleuritic chest pain developed. Pleurocentesis yielded 60 mL of yellow, cloudy fluid found to be exudative (WBC count, 15,300/cu mm,
Susceptibility loci for atopic dermatitis on chromosome 21 in a Swedish population
Authors: L. M. Bu, M. Bradley, C. Söderhäll, C. F. Wahlgren, I. Kockum, M. Nordenskjold
Journal: Allergy (2006)

Atopic dermatitis (AD) is a hereditary, pruritic, chronic, relapsing, inflammatory skin disease resulting from multiplex interactions between genes and environmental factors. We have previously found several loci showing suggestive linkage on chromosomes 3q14, 13q14, 15q14-15 and 17q21, and weaker linkage to chromosomes 1p32, 4q24-26 and 21q21 in 109 Swedish families.In order to confirm the linkage to chromosome 21, we carried out a replication linkage analysis with additional microsatellite markers on chromosome 21 in another set of 295 families.In the extended material, the Z-score was 2.40 (P < 7.4 x 10(-4)) in the region 21q21 for a semi-quantitative variable measurement; the severity of AD. When combining the two data sets into 404 families and stratifying according to asthma status, suggestive linkage was found only in the group of AD patients who also had asthma (Z-score 2.45, P < 7.4 x 10(-4) and 2.69, P < 7.4 x 10(-4)) in two different regions.Our results suggest that 21q21 could contain a susceptibility gene modulating the severity of AD especially in combination with asthma.
Choosing a Psychotherapist
Authors: Alfred Coodley
Journal: JAMA (1980)

<h3>To the Editor.—</h3> It appears that Nathan Schnaper, MD (242:327, 1979), thinks shopping is the key to choosing a psychotherapist. Well, I cannot say he is completely wrong, but I believe most patients have a somewhat better plan available to them. After all, a significant number of patients are referred by their internist or general practitioner, and said physician's choice of a psychotherapist is usually based on reasonably successful past performances with other patients who had been referred to that therapist. Still another source stems from physicians in any specialty having a personal acquaintanceship or friendship with one of the local therapists. I know, for example, that a number of the physicians in my medical building frequently have lunch together, with the result that we know one another well. Assuming, of course, that a rather positive impression is created and the necessity for a psychotherapy referral comes up, your lunch
Simultaneous development of Philadelphia chromosome-positive and -negative leukemias in the same patient
Authors: Sarit Assouline, Valerie Benemacher, Carlo Gambacorti-Passerini
Journal: American Journal of Hematology (2006)

To the Editor: Primary tonsillary lymphoma accounts for less than 1% of head and neck malignancies.Tonsillectomy is used to mainly establish the diagnosis and can be performed for localized small lesions.In general, the patients are treated by chemotherapy and/or radiotherapy [1,2].We present a 23-year-old woman who was referred to our ENT clinic with asymmetric tonsillary enlargement and acute bleeding.Tonsillectomy was performed.In paraffin sections; a tumor composed of large lymphoid cells that were positive for CD20, bcl-2, and p53 by immunohistochemistry was identified.Ki-67 index was roughly 80% (Figure 1).Polymerase chain reaction for immunoglobulin gene rearrangements was performed using DNA extracted from paraffin-embedded tissue and showed a single band indicating the presence of a clonal B cell proliferation.A diagnosis of ''Diffuse Large B Cell Lymphoma'' was rendered.No clinical or radiological evidence for tumor involvement in any other site was identified and the patient was accepted as Stage I clinically.The patient did not accept any further treatment.The patient was followed periodically every 6 months.Recurrence or systemic involvement was not observed during the 5-year-follow-up.This case is unusual since only tonsillectomy was curative.In general, radiation therapy is considered the primary mode of therapy for localized disease in tonsil lymphomas (stages I and II) [3,4].In one study, Jelic et al. reported a cure rate of 80% among their stage I NHL patients, who they followed without any therapy.In light of their experience as well as our observation, therapy options for localized NHL cases should be re-evaluated.
High-Resolution Imaging of the Optic Nerve and Retina in Optic Nerve Hypoplasia
Authors: Anastasia Pilat, Daniel Sibley, Rebecca J McLean, Frank A Proudlock, Irene Gottlob
Journal: Ophthalmology (2015)

To investigate the optic nerve and macular morphology in patients with optic nerve hypoplasia (ONH) using spectral-domain optical coherence tomography (SD OCT).
Genetic manipulation of genomes with rare-cutting endonucleases
Authors: Maria Jasin
Journal: Trends in Genetics (1996)

DNA double-strand breaks (DSBs) pose a threat to the genomic integrity of a cell. The failure to heal a break or the inappropriate repair of a break can result in the loss of genetic information and other potentially deleterious consequences, such as chromosomal translocations. Recent developments using rare-cutting endonucleases have allowed investigators to introduce one or a few DSBs into complex genomes. Such studies have begun to elucidate the complex mechanisms of nonhomologous and homologous repair used by mammalian cells to repair these lesions. A key finding is that gene targeting is stimulated two to three orders of magnitude by a DSB at the target locus. Thus, the use of rare-cutting endonucleases and the co-opting of cellular repair mechanisms might provide scientists with another tool for engineering changes into genomes.
Enhanced Generation of Helper T Type 1 and 2 Chemokines in Allergen-induced Asthma
Authors: Linying Liu, Nizar N. Jarjour, William W. Busse, Elizabeth A. B. Kelly
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Allergen-induced asthma is characterized by airway eosinophilia and recruitment of helper T (Th) Type 2 lymphocytes. We hypothesized that lymphocyte-associated chemokines contribute to allergen-induced airway inflammation. Sixteen subjects with asthma were phenotyped according to their response to inhaled antigen as single- or dual-phase responders, and then underwent bronchoscopy and segmental allergen bronchoprovocation. Bronchoalveolar lavage fluids were obtained before and 48 hours after segmental challenge with allergen to determine the cellular response and patterns of Th1 and Th2 chemokines and cytokines. Airway cells, cytokines, and lymphocyte-associated chemokines increased after segmental challenge. Th2 chemokines (thymus and activation-regulated chemokine, macrophage-derived chemokine) correlated with airway eosinophils and concentrations of interleukin-5 and -13. In contrast, airway lymphocytes correlated with both Th2 and Th1 (monokine-induced by IFN-gamma, IFN-gamma-inducible protein-10) chemokines. Notably, when subjects were analyzed according to the presence of a late-phase response, concentrations of both types of lymphocyte-associated chemokines were significantly greater in subjects with a dual-response phenotype. Our findings suggest that both Th2 and Th1 chemokines may be involved in allergen-induced airway inflammation. However, asthma subjects with a dual-responder phenotype have greater generation of chemokines that may lead to enhanced airway inflammation and obstruction after allergen exposure.
Case-control admixture mapping in Latino populations enriches for known asthma-associated genes
Authors: Dara G. Torgerson, Christopher R. Gignoux, Joshua M. Galanter, Katherine A. Drake, Lindsey A. Roth, Celeste Eng, Scott Huntsman, Raul Torres, Pedro C. Avila, Rocio Chapela, Jean G. Ford, José R. Rodríguez-Santana, William Rodríguez-Cintrón, Ryan D. Hernandez, Esteban G. Burchard
Journal: Journal of Allergy and Clinical Immunology (2012)
Salvador Minuchin: the `individual in context'
Authors: Beverly J. Montgomery
Journal: JAMA (1979)

Working in the 1940s in Israeli orphanages and in the 1950s in New York slums, Argentine-born psychiatrist Salvador Minuchin, MD, decided that too often Freudian psychoanalytic methods were not effective. There must be a better approach that could take into account the "systems" in which a person lived and interacted, he thought. And so, some unorthodox ideas began to germinate. Today, at 57, Minuchin probably is the best-known family therapist in the world. Director of the Philadelphia Child Guidance Clinic since 1965, he believes in changing the dysfunctional aspects of a family system instead of treating a person individually. Minuchin's ideas are provocative and in this age of mind-body medicine are of interest to many physicians. Applied in practice, they may offer a rewarding view of a patient's attitude toward sickness and toward optimal physical and psychological functioning. One of his primary credos is: The locus of pathology is the
Controversies in Clinical Care
Authors: William R. Best
Journal: JAMA (1982)

I believe the editors were trying to achieve the following objectives in soliciting the papers of this volume: (1) to focus on a number of important areas in medicine in which controversy over treatment still exists despite many published studies; (2) to distill key unanswered, specific questions out of these broader areas of therapeutic controversy; (3) to review salient features of design as well as published results relative to the better of relevant studies; (4) to critique these studies in terms of the suitability of experimental design and the consequent clinical believability of results; (5) to arrive at tentative recommendations relative to clinical practice; and (6) to make specific suggestions for experimental clinical studies to resolve lingering controversies. The component papers are all interesting and well written, but not uniform in their emphasis. The broad clinical areas covered and the scope of individual reviews (identified by the aforementioned numbers) are
Rhabdomyolysis from the Coadministration of Lovastatin and the Antifungal Agent Itraconazole
Authors: Robert S. Lees, Ann M. Lees
Journal: New England Journal of Medicine (1995)

To the Editor: Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, widely prescribed to treat hypercholesterolemia, are clearly effective and are associated with reductions in ...
Functional Recovery of Subepicardial Myocardial Tissue in Transmural Myocardial Infarction After Successful Reperfusion
Authors: Jan Bogaert, Alex Maes, Frans Van de Werf, Hilde Bosmans, Marie-Christine Herregods, Johan Nuyts, Walter Desmet, Luc Mortelmans, Guy Marchal, Frank E. Rademakers
Journal: Circulation (1999)

Background —The transmural extent of myocardial necrosis after an acute coronary artery occlusion can vary considerably. The contribution of residual subepicardial viable myocardium to global left ventricular function is largely unknown. Methods and Results —We studied 12 patients with single-vessel disease 1 week after successful reperfusion of a first transmural anterior myocardial infarction (MI). With PET, myocardial blood flow (MBF) and glucose metabolism were measured regionally, and the viability was graded as normal, mismatch, or match with severely (&lt;50% of normal) or intermediately (50% to 80% of normal) impaired MBF. Magnetic resonance tagging was used to regionally quantify fiber strains, wall thickening, and ejection fraction in patients 1 week and 3 months after the MI and in age-matched healthy volunteers. From 1 week to 3 months, subepicardial fiber shortening improved significantly in the match region (MBF &lt;50%, −5.1±7.0% to −9.9±8.7%; MBF of 50% to 80%, −7.1±7.6% to −14.9±7.9%). This was associated with an improvement in regional ejection fraction in the infarcted myocardium (29.6±21.8% to 43.5±15.5%, P &lt;0.0001) and in normal regions (54.3±15.1% to 56.5±13.1%, P =0.013), contributing to an increase in global ejection fraction from 44.2±22.2% to 49.3±17.9% ( P &lt;0.0001). Conclusions —Functional recovery of viable subepicardial regions is a mechanism of late improvement in regional and global ejection fraction after a so-called transmural MI.
Contraceptives on the N.H.S
Authors: A. Hart
Journal: BMJ (1973)

The provision of contraceptives on prescriptions may not be the forward-looking step that it appears to be at 1st sight.  It in no way provides for the needed adequate free family planning service which should include provision for education quite apart from regular medical examinations when the pill intrauterine device or cap is used.  Patients in areas well served by special clinics and local authority schemes (for example Lambeth and Aberdeen) would appear to be going to suffer by the proposed legislation.  The ability of general practice to meet the needs of a contraceptive service are limited by the many G.P.s the existence of a substantial group who are disinclined on religious or moral grounds to participate in such prescribing and the  number of doctors who feel that they are already overburdened in other areas of health care without adding to their work load (whatever fee the Government might envisage).  I would have been more reassured if Sir Keith Joseph had announced that the Government proposed to set up a free comprehensive family planning service based on existing clinics (such as those of the Family Planning Association and local  authorities).  I hope that as a profession we can make the Government aware of all the problesm involved so that yet more ill-conceived legislation does not follow premature and confused Ministry announcements.(FULL TEXT)
DECAMETHONIUM BROMIDE (C-10) IN ELECTRIC CONVULSIVE THERAPY
Authors: WILLIAM HOLT, MAX RINKEL, M. NICHOLSON, H. C. SOLOMON
Journal: American Journal of Psychiatry (1951)

Twenty-one mental patients were given decamethonium bromide to modify electric convulsive response. A dose of 4 mg. or above was necessary to prevent aggravation of pre-existing traumatic injury. Respiratory paralysis is regularly present when doses of 4 mg. or above are given. Pentothal sodium is useful to allay fear occasioned by muscle paralysis, but in sensitive persons pentothal may produce laryngeal spasm. Training in pentothal anesthesia and oxygen administration to unconscious patients is needed by the therapist wishing to use decamethonium bromide for the more serious physical contraindications to ECT. The therapeutic effect of ECT is not interfered with by decamethonium bromide modification of the seizure. Decamethonium bromide is a powerful and potentially dangerous drug, but it is of great value when skillfully used in trained hands.
Effect of synthesis parameters of the sol–gel-processed spray-dried silica gel microparticles on the release rate of dexmedetomidine
Authors: Pirjo Kortesuo, Manja Ahola, Minna Kangas, Mika Jokinen, Tiina Leino, Lauri Vuorilehto, Sirpa Laakso, Juha Kiesvaara, Antti Yli-Urpo, Martti Marvola
Journal: Biomaterials (2002)
Bone Morphogenetic Protein-6 Promotes Osteoblastic Prostate Cancer Bone Metastases through a Dual Mechanism
Authors: Jinlu Dai, Jill Keller, Jian Zhang, Yi Lu, Zhi Yao, Evan T. Keller
Journal: Cancer Research (2005)

Prostate cancer frequently metastasizes to bone where it forms osteoblastic lesions through unknown mechanisms. Bone morphogenetic proteins (BMP) are mediators of skeletal formation. Prostate cancer produces a variety of BMPs, including BMP-6. We tested the hypothesis that BMP-6 contributes to prostate cancer-induced osteosclerosis at bone metastatic sites. Prostate cancer cells and clinical tissues produced BMP-6 that increased with aggressiveness of the tumor. Prostate cancer-conditioned medium induced SMAD phosphorylation in the preosteoblast MC3T3 cells, and phosphorylation was diminished by anti-BMP-6 antibody. Prostate cancer-conditioned medium induced mineralization of MC3T3 cells, which was blocked by both the BMP inhibitor noggin and anti-BMP-6. Human fetal bones were implanted in severe combined immunodeficient mice and after 4 weeks, LuCaP 23.1 prostate cancer cells were injected both s.c. and into the bone implants. Anti-BMP-6 or isotype antibody administration was then initiated. Anti-BMP-6 reduced LuCaP 23.1-induced osteoblastic activity, but had no effect on its osteolytic activity. This was associated with increased osteoblast numbers and osteoblast activity based on bone histomorphometric evaluation. As endothelin-1 has been implicated in bone metastases, we measured serum endothelin-1 levels but found they were not different among the treatment groups. In addition to decreased bone production, anti-BMP-6 reduced intraosseous, but not s.c., tumor size. We found that BMP-2, BMP-4, BMP-6, and BMP-7 had no direct effect on prostate cancer cell growth, but BMP-2 and BMP-6 increased the in vitro invasive ability of prostate cancer cell. These data show that prostate cancer promotes osteoblastic activity through BMP-6 and that, in addition to its bone effects, suggest that BMPs promote the ability of the prostate cancer cells to invade the bone microenvironment.
Laboratory Control of Coumarin Anticoagulation: The Clinician's Dilemma.
Authors: M. J. Seide
Journal: Annals of Internal Medicine (1962)

s1 April 1962Laboratory Control of Coumarin Anticoagulation: The Clinician's Dilemma.M. J. Seide, M.D. (Assoc.)M. J. Seide, M.D. (Assoc.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-671_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince their introduction 20 years ago, coumarin-type drugs have become firmly established in clinical medicine. In the past ten years, the number of patients maintained on long-term therapy has increased phenomenally.The Quick prothrombin test is widely accepted by clinicians as a guide in determining the dose of coumarin. It is a bio-assay which requires meticulous technique, experienced technicians, and reliable reagents. More than one laboratory may be involved in the care of an individual patient, since treatment usually begins in the hospital during acute illness, then continues on an outpatient basis.To determine the validity, reproducibility, and reliability of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hartford, Conn. (CS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 671-671KeywordsCoumarinsDrugsOutpatient clinicsPatientsReproducibilityResearch laboratoriesTechnicians Issue Published: 1 April 1962 PDF downloadLoading ...
Race-Specific Differences in Antioxidant Enzyme Activity in Patients With Type 2 Diabetes
Authors: Karima Zitouni, Jaffar Nourooz-Zadeh, Diane Harry, Sally M. Kerry, D. John Betteridge, Francesco P. Cappuccio, Kenneth A. Earle
Journal: Diabetes Care (2005)

OBJECTIVE—Lipid hydroperoxide, a marker of oxidative stress, is linked to the development of nephropathy and is reportedly higher in patients of African origin compared with Caucasians. This may be relevant to race-specific differences in susceptibility to nephropathy. We investigated whether alterations in antioxidant enzyme activity could account for this biochemical phenotype and examined the relationship with conventional markers of renal disease. RESEARCH DESIGN AND METHODS—Two hundred seventeen individuals were studied. Patients with type 2 diabetes (n = 75) of African and Caucasian origin were matched by sex and racial origin with healthy control subjects (n = 142). Plasma total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were spectrophotometrically measured, and total cholesterol and triglycerides were measured by enzymatic methods. RESULTS—SOD activity was higher and GPx activity lower in patients with diabetes than in healthy control subjects (573 ± 515 vs. 267 ± 70 units/l, P &amp;lt; 0.001 and 150 ± 93 vs. 178 ± 90 units/l, P = 0.019, respectively). Patients of African origin with diabetes had lower GPx and higher SOD activity compared with Caucasian patients (126 ± 82 vs. 172 ± 97 units/l, P = 0.03 and 722 ± 590 vs. 445 ± 408 units/l, P = 0.002, respectively). Patients of African origin with normal urinary albumin excretion had significantly higher plasma creatinine concentrations (100.7 ± 14.2 vs. 88.1 ± 14.9 μmol/l, P = 0.007) and lower GPx activity (99.0 ± 72.4 vs. 173.7 ± 107.4 units/l, P = 0.02) compared with those of Caucasian origin. African origin was an independent predictor of elevated SOD (P = 0.007) and reduced GPx activity (P = 0.02) in regression analysis. CONCLUSIONS—SOD and GPx enzyme activities vary according to race and could account for differences in lipid hydroperoxide. In patients of African origin, susceptibility to renal disease may be associated with lowered GPx activity.