tbuckley/cabot-search huggingface dataset:
Abstract B58: The ATP-competitive mammalian target of rapamycin (mTOR) inhibitors suppress proliferation and induce apoptosis in the acquired rapamycin resistant breast cancer cells
Authors: Wu Tzung-Ju, Tsang Chi-Kwan, Zhang Yan-Jie, Zheng X.F. Steven
Journal: Clinical Cancer Research (2012)

Abstract The mammalian target of rapamycin (mTOR) is the major regulator of cell growth, metabolism and survival. The anti-cancer effect of allosteric mTOR-inhibitors, rapamycin and its analogs (rapalogs), has been tested extensively in different types of cancer cells. However, there is only limited clinical efficacy observed by treatment of these traditional mTOR inhibitors, partly due to the occurring of acquired rapamycin resistance (ARR). Several new mTOR inhibitors have been developed which specifically target to the catalytic sites of mTOR by competing with ATP binding, and are suggested to be more effective in inhibiting mTOR signaling and cell growth. However, their effect and mechanisms in ARR cells are not clear yet. In the present study, we used an in vitro model of acquired rapamycin-resistant (ARR) breast cancer cells to evaluate the efficacy of two major classes of ATP-competitive mTOR inhibitors, PI3K/mTOR dual and mTORC1/mTORC2 inhibitors. We found that ATP-competitive mTOR inhibitors acutely suppress the proliferation and prominently inhibit PI3K/mTOR signaling of ARR breast cancer cells. In contrast to the cytostatic effect of rapamycin, the ATP-competitive mTOR inhibitors induced apoptosis in ARR breast cancer cells. Unexpectedly, one of PI3K/mTOR dual inhibitors we tested, PI-103, only transiently inhibits its proposed signaling targets and the anti-proliferation effects are possibly mediated through the off-target mechanism. Our results support the rationale to use ATP-competitive mTOR inhibitors to treat rapamycin-resistant breast cancer cells and highlight the putative off-target effect of the new generation of mTOR inhibitor on cancer cells.
Classification of Lung Cancer—to be Revised
Authors: Milton B. Rosenblatt
Journal: JAMA (1967)

<h3>To the Editor:—</h3> The accuracy of lung cancer mortality data challenged inThe Journal(<b>198</b>:1374, 1966;<b>199</b>:674, 1967) may be considerably improved by the Eighth Revision of the International Classification of Causes of Death. The present nomenclature lists malignant neoplasm of bronchus and trachea and of lung, specified as primary (code No. 162), and malignant neoplasm of lung, unspecified as to whether primary or secondary (code No. 163). The latter category was always included in the tabulation of lung cancer mortality but uncertainty has existed as to whether the medical certifier had omitted primary specification because of the possibility that the pulmonary cancer was a metastasis from an occult extrathoracic primary site. Beginning Jan 1, 1968, there will be implemented a new nomenclature. All cases of lung cancer will be considered of primary origin (code No. 162) unless the certifier specifically designates that the tumor is of secondary
Light-Chain Proteinuria: Spurious False-Negative Reaction to Sulfosalicylic Acid
Authors: N. Stanley Nahman, Michael R. Murnane, William D. Kuehl, Lee A. Hebert, John C. Neff, William H. Bay
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 April 1985Light-Chain Proteinuria: Spurious False-Negative Reaction to Sulfosalicylic AcidN. STANLEY NAHMAN JR, M.D., MICHAEL R. MURNANE, M.D., WILLIAM D. KUEHL, M.D., LEE A. HEBERT, M.D., JOHN C. NEFF, M.D., WILLIAM H. BAY, M.D.N. STANLEY NAHMAN JR, M.D.Search for more papers by this author, MICHAEL R. MURNANE, M.D.Search for more papers by this author, WILLIAM D. KUEHL, M.D.Search for more papers by this author, LEE A. HEBERT, M.D.Search for more papers by this author, JOHN C. NEFF, M.D.Search for more papers by this author, WILLIAM H. BAY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-4-557_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We report the case of a patient with multiple myeloma and renal failure secondary to heavy urinary excretion of kappa light chains. This diagnosis was missed initially because the screening test for urinary light chains using sulfosalicylic acid was negative. However, we later discovered that the reaction of the patient's urine to sulfosalicylic acid was positive, but greatly delayed. Thus, the test for urinary light chains by sulfosalicylic acid we originally regarded as being a false-negative test provided, in reality, a spurious false-negative result.A 73-year-old man was referred to The Ohio State University Hospitals because of...References1. BAUR J. Clinical Laboratory Methods. 9th ed. St. Louis: C.V. Mosby Co.; 1982:686. Google Scholar2. SONNENWIRTHJARETT AL ed. Gradwohl's Clinical Laboratory Methods and Diagnosis. 8th ed. St. Louis: C.V. Mosby Co.; 1980:(I)485. Google Scholar3. FREEFREE AH. Urinalysis in Clinical Laboratory Practice. Boca Raton, Florida: CRC Press; 1975:51-6. Google Scholar4. PERRYKYLE MR. The clinical significance of Bence-Jones proteinuria. Mayo Clin Proc. 1975;50:234-8. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Ohio State University Columbus, OH 43210 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1985Volume 102, Issue 4Page: 557-558KeywordsExcretionMultiple myelomaProteinuriaRenal failureUrine Issue Published: 1 April 1985 PDF downloadLoading ...
The Relation of Gastroesophageal Reflux Disease and Its Treatment to Adenocarcinomas of the Esophagus and Gastric Cardia
Authors: Wong-Ho Chow
Journal: JAMA (1995)

To examine the relationship of gastrointestinal disorders and their treatment to the risk of adenocarcinomas of the esophagus and gastric cardia (AEC).A medical record-based case-control study, with data collected on a standardized form by a trained abstractor, blind to the case-control status.A large prepaid health plan.Case patients were plan members newly diagnosed with histologically confirmed AEC from 1986 to 1992. For each of the 196 eligible case patients, one control was selected who matched for membership at time of diagnosis, sex, year of birth, and duration of membership.Association between AEC and history of gastroesophageal conditions and their treatment. Conditional logistic regression procedures were used for calculation of odds ratios (ORs) and corresponding 95% confidence intervals (Cls), with adjustment for race, smoking status, and body mass index. Medications were grouped into H2 antagonists (cimetidine, ranitidine, famotidine, and nizatidine) and anticholinergics (propantheline bromide, dicyclomine hydrochloride, Donnatal [combination of atropine sulfate, hyoscyamine sulfate, phenobarbital, and scopolamine hydrobromide], and Librax [combination of chlordiazepoxide hydrochloride and clidinium bromide]).Significant twofold or greater risks of AEC were associated with a history of esophageal reflux, hiatal hernia, esophagitis/esophageal ulcer, and difficulty swallowing. The ORs increased with increasing number of these conditions. Although a fourfold risk was linked to four or more prescriptions for H2 antagonists, the risk was reduced to 1.5 (95% Cl, 0.4 to 5.4) after adjusting for the predisposing conditions. Further analysis revealed that the excess risk was restricted to persons with a history of gastroesophageal reflux and related conditions. No association was observed for overall use of anticholinergics. However, after adjustment for predisposing conditions, ORs decreased with increasing number of prescriptions for anticholinergics (P for trend = .08)This study provides reassuring findings that use of H2 antagonists and anticholinergics does not increase AEC risk. It also quantifies the elevated risk of AEC associated with gastroesophageal reflux disease. Further research into reflux disease and the production of premalignant epithelial changes may help elucidate carcinogenic mechanisms and measures aimed at early detection and prevention of AEC.
Thrombosis and Oral Contraceptives: Possible Predisposition
Authors: B. Astedt, S. Isacson, I. M. Nilsson, M. Pandolfi
Journal: BMJ (1973)

The coagulation factors and components of the fibrinolytic system were examined in 31 women with a previous history of phlebographically-verified thrombosis during the use of oral contraceptives of the combined type. Special attention was given to the histochemically-determined fibrinolytic activator content of the wall of biopsy specimens of superficial veins. None of the patients was taking contraceptives at the time of the investigation. Pathological changes, particularly in the fibrinolytic defence system, were found in most of the patients. They may be regarded as predisposed to thrombosis, and one might wonder whether these patients would sooner or later have had their thrombosis even if they had not used contraceptives. The concentration of antithrombin III was normal, indicating that this test is of no value for detecting patients predisposed to thrombosis, who should preferably not take oral contraceptives.
alpha 1-adrenergic agonists precondition rabbit ischemic myocardium independent of adenosine by direct activation of protein kinase C.
Authors: A Tsuchida, Y Liu, G S Liu, M V Cohen, J M Downey
Journal: Circulation Research (1994)

Ischemic preconditioning in the rabbit is initiated by adenosine A1-receptor stimulation, which activates protein kinase C (PKC). Additionally, alpha 1-adrenergic agonists can similarly protect ischemic myocardium, but there has been confusion about the role adenosine receptors play in this protection. To characterize the interaction between adrenergic and adenosine receptors and to study the possible role of PKC in this protection, we used isolated rabbit hearts perfused with oxygenated Krebs' buffer. All hearts were subjected to 30 minutes of regional myocardial ischemia and 2 hours of reperfusion. Infarct size was determined by triphenyltetrazolium staining. Pharmacologic preconditioning in hearts with a 5-minute phenylephrine (PE) infusion 10 minutes before the prolonged regional ischemia resulted in significantly smaller infarcts (9.7 +/- 1.3% of risk area) than in control hearts (31.0 +/- 2.6%, P &lt; .05). This protection could be effectively blocked by administration of the alpha-adrenergic blocker phenoxybenzamine. Methoxamine, an alpha 1a-selective agonist, failed to protect, whereas the alpha 1b-selective antagonist chloroethylclonidine aborted the protective effect of PE. Polymyxin B, an inhibitor of PKC, also blocked the protective effect of PE, implying that PKC has an important role in preconditioning. The adenosine receptor blocker 8-(p-sulfophenyl)theophylline (SPT) given at the same time as the PE infusion did not affect the protection, implying that an alpha 1-agonist could initiate protection independent of adenosine, presumably by direct coupling to PKC. However, the protective effect of PE could be blocked if SPT were administered during the 30-minute regional ischemia. This observation suggested that adenosine receptor occupancy is necessary during long ischemia to reactivate PKC and mediate the protection. However, the addition of a second PE infusion beginning 5 minutes before and continuing throughout the long ischemic period restored the protective effect of PE despite the presence of SPT. Thus, as long as at least one of the receptors (alpha 1-adrenegic or adenosine A1) is activated during long ischemia, protection will be realized. These data indicate that alpha 1 receptors do not precondition through an adenosine intermediate but that alpha 1-adrenergic and adenosine receptors activate parallel pathways within the myocyte that can trigger and mediate protection.
Exchange Transfusion as a Means of Removing Bilirubin in Haemolytic Disease of the Newborn
Authors: G. H. Lathe
Journal: BMJ (1955)

MwO JrjJMThere is no convincing evidence in the present series or in published cases to suggest that a longer remission of symptoms occurs after A.C.T.H. therapy than after any other treatment which succeeds.A.C.T.H. in no way avoids the expediency of all the other established methods in the assessment, treatment, and man- agement of the asthmatic case. SummaryThe use of adrenocorticotrophic hormone is described in 10 asthmatics.In eight of these there was a remark- able relief of severe acute respiratory distress, resistant to other forms of therapy.It is suggested that this substance should at present be used in asthma only as an emergency measure.
Metabolic predictors of middle-distance swimming performance.
Authors: J P Ribeiro, E Cadavid, J Baena, E Monsalvete, A Barna, E H De Rose
Journal: British Journal of Sports Medicine (1990)

To evaluate the capacity of different metabolic indices to predict performance in middle distance swimming, 15 competitive swimmers performed a submaximal and a maximal 400 metres freestyle swimming event. Expired gases were collected in Douglas bags immediately after the events for the determination of VO2 max. Arterialized blood samples were collected for the determination of maximal blood lactate concentration and the velocity corresponding to blood lactate concentration of 4 mM. The results demonstrated (means +/- SD): maximal velocity of 1.44 +/- 0.05 m.s-1; velocity at 85 percent of VO2 max of 1.36 +/- 0.04 m.s-1; velocity at 4 mM of 1.32 +/- 0.04 m.s-1; VO2 max of 3.47 +/- 0.5 l.min-1; maximal blood lactate concentration of 11.8 +/- 2.5 mM. Multiple regression analysis relating metabolic indices and maximal velocity demonstrated that only velocity at 85 percent of VO2 max (r2 = 0.81) and velocity at 4 mM (r2 = 0.79) were significant predictors. Thus, 79 percent of the variance in the performance of 400 m freestyle can be accounted for the velocity at 85 percent of VO2 max or the velocity at 4 mM. The success in this event seems to depend on the swimmer's capacity to achieve higher velocities with lower blood lactate levels and/or utilizing a lower percentage of their VO2 max.
Effect of drink temperature on antropyloroduodenal motility and gastric electrical activity in humans.
Authors: W M Sun, R Penagini, G Hebbard, C Malbert, K L Jones, S Emery, J Dent, M Horowitz
Journal: Gut (1995)

There is little information on the motor mechanisms underlying the effects of meal temperature on gastric emptying. The effects on antropyloric pressures and the surface electrogastrogram of ingesting drinks at 4 degrees C, 37 degrees C, and 50 degrees C (350 ml normal saline and 50 ml low calorie (7 kj) orange cordial) given in randomised order were measured over 60 minutes in 12 normal volunteers (10 men and 2 women, aged 18-55 years). The warm and cold drinks suppressed antral pressure waves (p < 0.05), altered the organisation of antropyloric pressure waves (p < 0.05), stimulated isolated pyloric pressure waves (p < 0.05), and increased electrogastrogram frequency (p < 0.05) when compared with the 37 degrees C drink. These changes were greatest in the first 30 minutes after ingestion and greater (p < 0.05) with the 4 degrees C drink. Temperature has major effects on postprandial antropyloroduodenal motility in normal subjects. Both cold and warm drinks stimulate a pattern of motility associated with retardation of transpyloric flow.
Hydroxylated Metabolites of Polybrominated Diphenyl Ethers in Human Blood Samples from the United States
Authors: Xinghua Qiu, Robert M. Bigsby, Ronald A. Hites
Journal: Environmental Health Perspectives (2008)

A previous study from our laboratory showed that polybrominated diphenyl ethers (PBDEs) were metabolized to hydroxylated PBDEs (HO-PBDEs) in mice and that para-HO-PBDEs were the most abundant and, potentially, the most toxic metabolites.The goal of this study was to determine the concentrations of HO-PBDEs in blood from pregnant women, who had not been intentionally or occupationally exposed to these flame retardants, and from their newborn babies.Twenty human blood samples were obtained from a hospital in Indianapolis, Indiana, and analyzed for both PBDEs and HO-PBDEs using electron-capture negative-ionization gas chromatographic mass spectrometry.The metabolite pattern of HO-PBDEs in human blood was quite different from that found in mice; 5-HO-BDE-47 and 6-HO-BDE-47 were the most abundant metabolites of BDE-47, and 5'-HO-BDE-99 and 6'-HO-BDE-99 were the most abundant metabolites of BDE-99. The relative concentrations between precursor and corresponding metabolites indicated that BDE-99 was more likely to be metabolized than BDE-47 and BDE-100. In addition, three bromophenols were also detected as products of the cleavage of the diphenyl ether bond. The ratio of total hydroxylated metabolites relative to their PBDE precursors ranged from 0.10 to 2.8, indicating that hydroxylated metabolites of PBDEs were accumulated in human blood.The quite different PBDE metabolite pattern observed in humans versus mice indicates that different enzymes might be involved in the metabolic process. Although the levels of HO-PBDE metabolites found in human blood were low, these metabolites seemed to be accumulating.
Sulfonylurea Treatment of Type 2 Diabetic Patients Does Not Reduce the Vasodilator Response to Ischemia
Authors: Paolo Spallarossa, Mara Schiavo, Pierfranco Rossettin, Stefano Cordone, Luca Olivotti, Renzo Cordera, Claudio Brunelli
Journal: Diabetes Care (2001)

OBJECTIVE—Sulfonylureas block the activation of vascular potassium-dependent ATP channels and impair the vasodilating response to ischemia in nondiabetic individuals, but it is not known whether this occurs in type 2 diabetic patients under chronic treatment with these drugs. Glimepiride, a new sulfonylurea, apparently has no cardiovascular interactions. The aim of our study was to compare the effect of the widely used compound glibenclamide, the pancreas-specific glimepiride, and diet treatment alone on brachial artery response to acute forearm ischemia. RESEARCH DESIGN AND METHODS—Brachial artery examination was performed by a high-resolution ultrasound technique on 20 type 2 diabetic patients aged (mean ± SD) 67 ± 2 years and on 18 nondiabetic patients matched for age, hypertension, and dislipidemia. Diabetic subjects underwent three separate evaluations at the end of each 8-week treatment period, during which they received glibenclamide, glimepiride, or diet alone according to crossover design. Scans were obtained before and after 4.5 min of forearm ischemia. Postischemic vasodilation and hyperemia were expressed as percent variations in vessel diameter and blood flow. RESULTS—Postischemic vasodilation and hyperemia were, respectively, 5.42 ± 0.90 and 331 ± 38% during glibenclamide, 5.46 ± 0.69 and 326 ± 28% during glimepiride, and 5.17 ± 0.64 and 357 ± 35% during diet treatment (NS). These results were similar to those found in the nondiabetic patients (6.44 ± 0.68 and 406 ± 42%, NS). CONCLUSIONS—In type 2 diabetic patients, the vasodilating response to forearm ischemia was the same whether patients were treated with diet treatment alone or with glibenclamide or glimepiride at blood glucose–lowering equipotent doses.
The Technologies of Time Measurement: Implications at the Bedside and the Bench
Authors: Stanley Joel Reiser
Journal: Annals of Internal Medicine (2000)

This essay explores how chronologically linked indices of health and illness, such as variation in body temperature, achieved clinical and scientific significance. It shows why time has been a potent concept through which key associations among the data of medicine are ordered and revealed, and it examines the graphical and case reporting methods of organizing evidence that made such associations possible.
Several Different Cell Surface Molecules Control Negative Selection of Medullary Thymocytes
Authors: Hidehiro Kishimoto, Jonathan Sprent
Journal: The Journal of Experimental Medicine (1999)

Repeated attempts to show that costimulation for negative selection is controlled by a single cell surface molecule have been unsuccessful. Thus, negative selection may involve multiple cell surface molecules acting in consort. In support of this idea, we show here that at least three cell surface molecules, namely CD28, CD5, and CD43, contribute to Fas-independent negative selection of the tolerance-susceptible population of heat-stable antigen (HSA)hiCD4+8− cells found in the medulla. The costimulatory function of these three molecules can be blocked by certain cytokines, IL-4 and IL-7, and coinjecting these cytokines with antigen in vivo abolishes negative selection; Fas-dependent negative selection, however, is maintained. The results suggest that efficient negative selection requires the combined functions of at least four cell surface molecules: CD28, CD5, CD43, and Fas.
Neomycin Contact Dermatitis Superimposed on Otitis Externa
Authors: C. Owen Jensen
Journal: JAMA (1966)

ALLERGIC sensitization to topically applied neomycin was first reported by Baer and Ludwig in 1952. 1 Their patient had otitis externa treated with neomycin, which was not typical of an acute contact dermatitis, but consisted of an exacerbation of the otitis externa. Since that time there have been several reports describing clinical patterns of neomycin sensitivity. However, the original theme of a gradually worsening dermatitis, or flares of an underlying dermatitis with treatment, characterizes most reports. Otitis externa was one of the most frequent conditions with which neomycin sensitivity was associated. 2-4 Familiar as these facts may be to the dermatologist, we feel that it has not been sufficiently emphasized in the literature reaching nondermatologists who are likely to treat the vast majority of patients with otitis externa.  Materials and Methods  Patch testing was performed on all patients generally following the method of Epstein. 5 One drop of 20% aqueous
Successful treatment of a patient with cardiac lymphoma who presented with a complete atrioventricular block
Authors: Mitsuyuki Nagano, Naokuni Uike, Junji Suzumiya, Koichiro Muta, Tatsuro Goto, Youko Suehiro, Ilseung Choi, Yuji Yufu, Jun-ichi Taniguchi, Masahiro Kikuchi, Mitsuo Kozuru
Journal: American Journal of Hematology (1998)

A patient with primary cardiac lymphoma, which is very rare, generally is regarded to have a poor prognosis. We herein report a patient with cardiac lymphoma who was treated successfully by systemic chemotherapy and radiotherapy using a pacemaker to control the complete atrioventricular (A-V) block. A 70-year-old man had a syncope caused by a complete A-V block. An echocardiogram, a computed tomographic scan, and magnetic resonance imaging of his chest showed a cardiac tumor. At this time, a biopsy of the cardiac tumor disclosed malignant lymphoma (diffuse large cell type, B cell type). The patient was thus treated with systemic chemotherapy and radiotherapy and, as a result, achieved a complete remission with a disappearance of the A-V block. Recently, several successful outcomes involving primary cardiac lymphoma have been reported because of the progress in diagnostic techniques including echocardiography, computed tomographic scanning, and magnetic resonance imaging, as well as improvement in the therapy of malignant lymphoma. Our clinical experience indicated that an early and accurate diagnosis combined with the appropriate therapy can thus help in obtaining a long survival in patients with primary cardiac lymphoma. Am. J. Hematol. 59:171–174, 1998. © 1998 Wiley-Liss, Inc.