tbuckley/cabot-search huggingface dataset:
Abstract A25: Humanized immunoenzyme with enhanced activity for glucuronide prodrug activation in the tumor microenvironment
Authors: Kaichuan Chen, Yu-lin Leu, Zeljko M. Prijovich, Steve Roffler
Journal: Clinical Cancer Research (2010)

Abstract Antibody-directed enzyme prodrug therapy (ADEPT) is one of potential therapies to overcome systemic toxicity caused by traditional chemotherapy. Our lab have designed and developed glucuronide prodrugs that can be converted to potent antineoplastic agents by β-glucuronidase (βG). Toxic drugs can be preferentially generated at the tumor site after βG is first targeted to tumor cells as an antibody-enzyme fusion protein (immunoenzyme). For utilization of this therapeutic strategy in clinic, the immunoenzyme need to be compatible with humans. We have recently employed directed evolution to generate a human βG mutant (S2) that enhanced activity at neutral pH. To investigate if the S2 variant would be beneficial for tumor-selective prodrug activation, a humanized cc49 scFv gene with specificity for the TAG-72 tumor-associated antigen was fused to the wild-type hβG or S2 genes to create hcc49-hβG and hcc49-S2, respectively. Here, we show that immunoenzymes have 100-folds lower KD than hcc49 scFv and retain enzymatic activities as wild-type hβG and S2 mutant proteins. In in vitro cytotoxicity assay, the data demonstrated that hcc49 immunoenzymes can preferentially activate glucuronide prodrugs at TAG-72 positive cells, and hcc49-S2 was about 10-fold more effective than hcc49-hβG as indicated by a lower IC50 value. Further in vivo experiment, we will examine if the enhanced immunoenzyme have better efficacy to hydrolyze anticancer glucuronide prodrugs at physiological condition. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A25
Expression of adhesion molecules on cord‐blood‐derived, cultured human mast cells and effect of dexamethasone on intercellular adhesion molecule‐1 expression on the mast cells treated by phorbol myristate acetate
Authors: H. Inamura, M. Kurosawa, T. Kuwasaki, Y. Kamada, H. Kayaba, J. Chihara
Journal: Allergy (2001)

Background: Increase in mast‐cell number at sites of allergic inflammation has been observed, and glucocorticoids applied to the sites have been shown to result in a significant reduction in mast cells. However, the expression of adhesion molecules on cultured human mast cells and their regulation by glucocorticoids is poorly understood. Methods: Cultured human mast cells were raised from human umbilical cord‐blood cells, and the expression of adhesion molecules on the mast cells was analyzed by flow cytometry. The cells were also incubated with 10 ng/ml phorbol myristate acetate (PMA) for the indicated time, and the effect of dexamethasone on adhesion molecule expression on PMA‐treated, cultured human mast cells was examined. Results: Cord‐blood‐derived, cultured human mast cells constitutively expressed intercellular adhesion molecule‐1 (ICAM‐1), very late antigen‐4 (VLA‐4), and macrophage‐1 antigen (Mac‐1). Weak expression of lymphocyte function‐associated antigen‐1 (LFA‐1) was observed on the cells, whereas they failed to express vascular cell adhesion molecule‐1 (VCAM‐1). Kinetic studies showed that after a transient downregulation reaching a minimum at 8 h, the expression of ICAM‐1 was markedly upregulated on PMA‐treated mast cells after a 24‐h incubation. In contrast, the expression of VLA‐4 and Mac‐1 was decreased after the incubation with PMA for 24 h. The PMA‐induced upregulation of ICAM‐1 was inhibited by dexamethasone in a concentration‐dependent manner. Conclusions: Our results indicate that cord‐blood‐derived, cultured human mast cells constitutively express integrins and ICAM‐1, but not VCAM‐1, and demonstrate for the first time that dexamethasone inhibits the upregulation of ICAM‐1 on PMA‐treated, cultured human mast cells.
Body weight and arterial hypertension: Authors' reply
Authors: S. Sonne-Holm, T. I A Sorensen, G. Jensen, P. Schnohr
Journal: BMJ (1989)

except in a hope that domiciliary fetal monitoring will promote more rational and convenient moni- toring policies.56We agree that there is a risk of overuse,4 and we are sure the debate on the value of antenatal cardiotocographs and the mission to deliver healthy babies should continue in the widest context.Meanwhile, we fully support any call for further evaluation of domiciliary fetal monitoring, and we have recently embarked on a major collaborative research programme in the south Wales valleys.This new application is potentially useful and deserves a fair hearing.
Book: Medicine and the German Jews: A History
Authors: A. Paton
Journal: BMJ (2001)

John M Efron Yale University Press, £27.50, pp 343 ISBN 0 300 08377 7 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> In the Middle Ages half of all doctors in western Europe were Jewish. They held positions of power in the royal courts and among the Christian clergy. In theory the populace was forbidden to consult them, and a series of bans between 1246 and … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Expert Panel vs Decision-Analysis Recommendations for Postdischarge Coronary Angiography After Myocardial Infarction
Authors: Karen M. Kuntz
Journal: JAMA (1999)

ContextExpert panels and decision-analytic techniques are increasingly used to determine the appropriateness of medical interventions, but these 2 approaches use different methods to process evidence.ObjectiveTo compare expert panel appropriateness ratings of coronary angiography after myocardial infarction (from the time of hospital discharge to 12 weeks after infarction) with the health gains and cost-effectiveness predicted by a decision-analytic model.DesignComparison of the degree of importance of the clinical variables considered in expert panel appropriateness ratings vs a previously published decision-analytic model. Identification of 36 clinical scenarios from the expert panel that could be simulated by the decision-analytic model.Main Outcome MeasuresAppropriateness score and appropriateness classification (expert panel) vs gain in quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (decision-analytic model).ResultsThe most important clinical variables were similar in the 2 approaches, with the exercise tolerance test result exerting the greatest leverage on strength of recommendation for angiography. Among the expert panel clinical scenarios considered to be appropriate for coronary angiography that could be simulated in the decision-analysis model, the median (interquartile range) health gain and incremental cost-effectiveness ratio were 0.59 (0.41-0.76) QALYs and $27,000 ($23,000-$35,000) per QALY gained, respectively. Among the clinical scenarios that expert panels considered inappropriate, the corresponding medians (interquartile ranges) were 0.24 (0.19-0.34) QALYs and $54,000 ($36,000-$58,000) per QALY gained. The Spearman rank correlation between appropriateness score and QALY gain was 0.58 (P<.001) and between appropriateness score and estimated incremental cost-effectiveness ratios was −0.66 (P<.001).ConclusionsFor the 36 expert panel scenarios that could be simulated by the decision-analytic model, there was moderate to good agreement between the appropriateness score and both the health gain and the incremental cost-effectiveness ratio of coronary angiography compared with no angiography in the convalescent phase of acute myocardial infarction, but several scenarios judged as inappropriate by the expert panel approach had cost-effectiveness ratios comparable with many generally recommended medical interventions. Formal synthesis of expert judgment and decision modeling is warranted in future efforts at guideline development.
Allergy to Human Seminal Plasma
Authors: Bernard B. Levine, Reuben P. Siraganian, Isaac Schenkein
Journal: New England Journal of Medicine (1973)

THE infrequency of the syndrome of allergy to human ejaculate1 prompts us to report another such case. In addition, we present immunologic data including histamine release, and the finding that the antigen is a relatively low-molecular-weight constituent of seminal plasma, present in seminal plasmas of all 15 men tested.Case ReportA 29-year-old married woman, seen in May, 1972, had been essentially healthy except for ragweed hay fever of 15 years' duration. In May, 1971, within 1 hour after intercourse, her eyes became itchy and severely swollen, and nasal congestion and sneezing developed. The symptoms and signs gradually subsided over . . .
Inhibition of murine granulopoiesis in vitro by dexamethasone
Authors: David W. Golde, Noelle Bersch, Shirley G. Quan, Martin J. Cline
Journal: American Journal of Hematology (1976)

Abstract The effect of dexamethasone on mouse bone marrow granulocyte‐monocyte precursor cells (CFU‐C) was studied in vitro. Dexamethasone inhibited colony formation in the presence of maximally stimulating concentrations of colony‐stimulating activity. A mean colony reduction of 55% occurred at 10 9 M dexamethasone and inhibition was observed at concentrations as low as 10 −12 M. The dexamethasone suppression could be abrogated by progesterone. These studies provide evidence that the committed granulocyte‐monocyte stem cell has a glucocorticoid receptor mechanism that when activated results in inhibition of cellular proliferation in vitro.
Acute Haemolytic Anaemia
Authors: J. P. Currie
Journal: BMJ (1944)

MEDICAL JSURNHL limb are, when possible, the best treatment for the paralysed muscles.and prevent the development of painful stiffness and various forms of neurotic hesitation in using the limb.In high median lesions passive flexion of the index finger is especially important to avoid stiffness of this finger in extension.In wounds of the brachial plexus the use of a sling and a soft pad in the axilla, if the deltoid is paralysed, combined with regular movements, is all the treatment of the resulting paralysis required during the first two .or three weeks until the case reaches a special centre.Lower Extremity.-Theearly treatment of injuries to the nerves of the lower extremity consists simply in maintaining, if possible, the range of movement-of the joints.The only support likely to be required is for drop-foot, and, unlike that of the upper extremity, this palsy should be supported as soon as possible.A cradle should be used to relieve the pressure of bed-clothes and to allow movement of the limb.If the sole of the foot is anaesthetic it must be protected from injury, and when there is sufficient recovery to allow walking it is important to provide only well-fitting light boots without irregu- larities of the sole.The patient should be told of this need to protect anaesthetic skin from both injury and burns.Finally, as with all traumatic war surgery, it must be stressed that attention to the morale of the patient is most important.As the medical officer has little time to give individual attention to cases of nerve injury, much depends on the massage depart- ment.The well-handled man is obviously keen to overcome his disability as much as possible.He moves the joints with vigour and confidence, and maintains the maximum use of his injured limb.Summary Quick neurological methods of examining wounded limbs for nerve injury, suitable for use by.surgeons in a forward battle area, are described and illustrated.Simple methods of recording are given.In early treatment the dangers of splinting the fingers are emphasized.Early active or passive movement is valuable.Con- tinual full relaxation of paralysed muscles is harmful.Our thanks are due to Col. R.
Morphological determinants of echocardiographic patterns of mitral valve systolic anterior motion in obstructive hypertrophic cardiomyopathy.
Authors: H G Klues, W C Roberts, B J Maron
Journal: Circulation (1993)

The morphological determinants of mitral valve systolic anterior motion (SAM) and obstruction to left ventricular outflow in patients within the broad clinical spectrum of hypertrophic cardiomyopathy (HCM) are not completely understood, particularly the contribution of mitral leaflet length and size.To clarify this issue, mitral valve specimens from 43 patients with HCM and basal outflow obstruction were used to relate morphometric measurements of leaflet area to certain morphological and functional assessments of left ventricular outflow tract geometry and valvular motion obtained from echocardiograms in the same patients. Twenty-four patients (56%) had mitral valves of normal size (leaflet area < 12.0 cm2) and 19 patients (44%) had enlarged and elongated valves (area > or = 12.0 cm2). Compared with normal-sized mitral valves, the enlarged valves were situated more posteriorly in a larger left ventricular outflow tract (cross-sectional area, 3.3 +/- 1.0 versus 1.9 +/- 0.7 cm2 for normal-sized valves; p < 0.001) and also had greater systolic excursion of the anterior leaflet (16.2 +/- 4.5 versus 13.3 +/- 3.3 mm, p < 0.02), usually with a distinctive sharp-angled bend and localized contact of the leaflet tip with ventricular septum ("typical" SAM); this pattern of SAM was possible because the central and distal portions of the leaflet were relatively free of fibrous thickening. In contrast, normal-sized mitral valves were situated more anteriorally in a smaller left ventricular outflow tract and frequently showed a different mechanism of SAM and subaortic obstruction with relatively limited leaflet motion, absence of a sharp bend, and septal contact involving more substantial portions of the anterior leaflet and contiguous chordae ("atypical" SAM); mitral-septal apposition was effected in large measure by posterior ventricular septal motion. This pattern of SAM was invariably associated with a more diffuse pattern of fibrous thickening.Patients with obstructive HCM show patterns of mitral valve SAM that are diverse and determined largely by the interrelation of left ventricular outflow tract geometry, the size and mobility of the mitral leaflets, and the presence and distribution of fibrous thickening.
Hypoplastic Anemia and Carbamazepine Therapy
Authors: N. H. Dyer
Journal: JAMA (1967)

<h3>To the Editor:—</h3> I read with interest "Use of Carbamazepine in Epilepsy" by Livingston et al (<b>200</b>: 204, 1967) and noted their reports of further cases of hematopoietic disturbance following the administration of this drug. The authors refer to a nonfatal case of hypoplastic anemia attributed to carbamazepine by me and my colleagues.<sup>1</sup>This case was subsequently described in more detail,<sup>2</sup>and in the discussion of the then documented cases attention was drawn to the long duration of treatment and large total dose administered. However, I have never believed that these factors were solely responsible, as many sufferers from trigeminal neuralgia have been treated in the United Kingdom with similar quantities of the drug without developing bone marrow failure. Therefore, individual susceptibility or some other factor must be involved. I know of no published studies on the mechanism of the hematopoietic disturbance. As these blood dyscrasias have been
Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro.
Authors: K Y Tsang, H H Fudenberg, G M Galbraith, R P Donnelly, L R Bishop, W R Koopmann
Journal: Journal of Clinical Investigation (1985)

The in vitro effects of isoprinosine (ISO) on interleukin-2 (IL-2) production, the expression of Tac antigen (IL-2 receptor) on lymphocytes, and the ability of Leu 3(+) cells to absorb interleukin-1 (IL-1) were investigated in 10 patients with acquired immune deficiency syndrome (AIDS). In 9 of the 10 patients, production of IL-2 from mononuclear cells and Leu 3(+) cells was depressed; expression of Tac antigen on mononuclear cells and Leu 2(+) cells was found to be depressed in 9 of 10 patients. The ability of the Leu 3(+) lymphocytes to absorb IL-1 was depressed in all (four of four) patients studied. After ISO treatment, IL-2 production, Tac antigen expression and IL-1 absorption were restored to normal or near normal levels in most of the patients. These results suggest that ISO has an immunostimulating capacity in AIDS patients and that the potential of ISO in immune response restoration in AIDS patients deserves critical consideration.
The gut connectome: making sense of what you eat
Authors: Diego V. Bohórquez, Rodger A. Liddle
Journal: Journal of Clinical Investigation (2015)

The enteric nervous system has been studied thus far as an isolated unit. As researchers probe deeper into the function of this system, it is evident that the neural network stretches beyond enteric neurons. It is formed by both intrinsic and extrinsic neurons innervating the gut, enteric glia, and innervated sensory epithelial cells, such as enteroendocrine cells. This Review series summarizes recent knowledge on function and disease of nerves, glia, and sensory epithelial cells of the gut in eight distinctive articles. The timing and growing knowledge for each individual field calls for an appropriate term encompassing the entire system. We call this neuronal ensemble the “gut connectome” and summarize the work from a food sensory perspective.
Myocardial Muscarinic Receptor Upregulation and Normal Response to Isoproterenol in Denervated Hearts by Familial Amyloid Polyneuropathy
Authors: Nicolas Delahaye, Dominique Le Guludec, Sylvie Dinanian, Jacques Delforge, Michel S. Slama, Laure Sarda, Frédéric Dollé, Hichem Mzabi, Didier Samuel, David Adams, André Syrota, Pascal Merlet
Journal: Circulation (2001)

Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy. The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia. Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated.Twenty-one patients were studied (age, 39+/-11 years; normal coronary arteries; left ventricular ejection fraction 68+/-9%). To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with (11)C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used. Cardiac beta-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step). The mean muscarinic receptor density was higher in patients than in control subjects (B'(max), 35.5+/-8.9 versus 26.1+/-6.7 pmol/mL, P=0.003), without change in receptor affinity. The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (DeltaHR after atropine, 11+/-21% versus 62+/-17%; P<0.001), consistent with parasympathetic denervation. Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects.Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac beta-receptor responsiveness to catecholamines.
Ovarian and cervical cancer.
Authors: C. Williams
Journal: BMJ (1992)

Death rates from cervical cancer have already fallen this century and for patients with invasive cervical cancer five year survival rates are greater than for most solid tumours. Better screening for premalignant changes may further reduce the incidence of invasive cancer; indeed, it has been claimed that the reduction in mortality could be as high as 90%, though estimates of screening efficacy have varied greatly. For those with advanced invasive carcinoma neoadjuvant chemotherapy may reduce the risk of relapse and improve survival.
Abdominal Pain in Diabetic Metabolic Decompensation
Authors: Ian W. Campbell
Journal: JAMA (1975)

Severe abdominal pain and tenderness occured in 46 of 211 episodes of severe diabetic metabolic decompensation. No association was found between abdominal pain and the degree of dehydration or the initial blood glucose level. In 17 instances, the abdominal pain could be attributed to the precipitating cause of the metabolic decompensation. The episodes of unexplained pain all occurred insulin-dependent patients less than 40 years of age; of these, only three had a plasma bicarbonate level greater than 10 mEq/liter, and in two patients, additional factors could account for the relative lack of ketoacidosis. Abdominal pain occurring in patients more than 40 years old, irrespective of the plasma bicarbonate level, and in patients of any age with a plasma bicarbonate level in excess of 10 mEq/liter, almost invariably indicates a specific underlying cause.
Challenges of Do-Not-Attempt-Resuscitation Orders—Reply
Authors: Craig D. Blinderman, Eric L. Krakauer, Mildred Z. Solomon
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
California Public Hospitals&lt;subtitle&gt;The Buck Has Stopped&lt;/subtitle&gt;
Authors: Emily Friedman
Journal: JAMA (1997)

It is often said that California is the most trend-setting state in the nation; what happens first there is supposed to happen soon after in other places. There is ample evidence that this is the case with health care. California has been far ahead of the national curve in the restructuring of the health care system, penetration by managed care, and creative (to say the least) financing of public health services. California also requires each county to ensure that health care is available to medically indigent legal residents. For decades, that commitment was expressed through county hospitals; in 1964, of 58 counties in the state, 49 had at least 1 public hospital, for a total of 66. Today, the number is 24 hospitals in 17 counties, and both numbers will likely drop further this year; facilities in Los Angeles, Merced, San Luis Obispo, and Stanislaus counties are facing potential closure
The evolutionary psychology of patriarchy: Women are not passive pawns in men's game
Authors: David M. Buss, Joshua Duntley
Journal: Behavioral and Brain Sciences (1999)

We applaud Campbell's cogent arguments for the evolution of female survival mechanisms but take issue with several key conceptual claims: the treatment of patriarchy; the implicit assumption that women are passive pawns in a male game of media exploitation; and the neglect of the possibility that media images exploit existing evolved psychological mechanisms rather than create them.
CHEMICAL, CLINICAL, AND IMMUNOLOGICAL STUDIES ON THE PRODUCTS OF HUMAN PLASMA FRACTIONATION. XII. THE USE OF CONCENTRATED NORMAL HUMAN SERUM GAMMA GLOBULIN (HUMAN IMMUNE SERUM GLOBULIN) IN THE PREVENTION AND ATTENUATION OF MEASLES 12
Authors: C. W. Ordman, C. G. Jennings, C. A. Janeway
Journal: Journal of Clinical Investigation (1944)