tbuckley/cabot-search huggingface dataset:
Social Catastrophe: Orphaned by AIDS
Authors: Linda Hawes Clever
Journal: JAMA (1993)

<h3>To the Editor.</h3> —Michaels and Levine<sup>1</sup>present troubling and persuasive data about human immunodeficiency virus (HIV)— related orphans in the United States. Nicholas and Abrams<sup>2</sup>endorse their findings. It is essential to note that the best way to avoid the impending "social catastrophe," sorrows, and lost promise associated with HIV orphans is to prevent HIV infection in women. Effective HIV prevention programs for women must be established now.
Nervous System Toxic Effects of Cancer Therapy
Authors: Itzhak D. Goldberg
Journal: JAMA (1982)

SERIOUS damage to the nervous system from radiation therapy or chemotherapy is uncommon, and its pathogenesis is poorly understood. Although there are numerous elaborate descriptions of neuropathological changes, the relevant definition of tolerance to these modes of therapy is based on function. Recently, thresholds for serious neurological damage have begun to be established through clinical observations and experiments with animal models. <h3>RADIATION TOXICITY</h3> The precise targets and mechanisms involved in neurological injury from ionizing radiation are complex. Intrinsic neural tissue seems to be more resistant to radiation injury than the supporting glial tissue and capillary endothelium; in late radiation injury in particular, damage to small and medium vascular arterioles is considered to be the etiology.<sup>1-4</sup>When neurological damage occurs, blood vessel abnormalities—including hyalinization, fibrinoid necrosis of the vessel walls, luminal obliteration, and thrombosis—are prominent in both the damaged area of the brain and the surrounding normal tissue. Demyelination is
Pruritus in polycythemia vera is associated with a lower risk of arterial thrombosis
Authors: Naseema Gangat, Jacob J. Strand, Terra L. Lasho, Chin‐Yang Li, Animesh Pardanani, Ayalew Tefferi
Journal: American Journal of Hematology (2008)

Among 418 patients with polycythemia vera seen at our institution and in whom pruritus history was recorded, the presence of pruritus at diagnosis was documented in 131 (31%) and its absence in 287 (69%). Pruritus was less frequently reported by smokers (12% vs. 24%; P = 0.004) and diabetics (5% vs. 11%; P = 0.04). The presence of pruritus was associated with a lower rate of arterial thrombosis, both at diagnosis (8% vs. 17%; P = 0.01) and during follow-up (16% vs. 30%; P = 0.003). Multivariable analysis revealed that these associations were independent of other risk factors for thrombosis. High JAK2V617F allele burden clustered with pruritus (P = 0.002) but did not affect thrombosis rates.
Effect of IgG anti‐Rh<sub>o</sub>(D) in adult patients with chronic autoimmune thrombocytopenia
Authors: A. Salama, V. Kiefel, C. Mueller‐Eckhardt
Journal: American Journal of Hematology (1986)

Abstract Seventeen adult patients with chronic (15 cases) or acute (two cases) autoimmune thrombocytopenia (ITP) were given intravenous and/or intramuscular injections of 0.75–4.5 mg of IgG anti‐Rh o (D) over a period of 1–5 days. Significant elevations of the platelet count (increments &gt; 50 × 10 9 /liter) resulted in 13 of 15 Rh‐positive patients but not in either of two Rh‐negative patients. Heat‐aggregated human albumin given to one of the Rh‐negative patients also did not lead to a significant increase of the platelet count. The elevation of the platelet counts in Rh‐positive patients after IgG anti‐Rh o (D) administration was often transient (&lt; 4 weeks), but long‐term benefit (&gt; 5 months) was achieved in five cases. The IgG concentration on RBC from five Rh‐positive patients studied increased from a usually undetectable value before to ∼ 700–1,700 IgG molecules/per RBC after anti‐Rh o D) administration resulting in a strongly positive direct antiglobulin test. Nevertheless, an overt clinical hemolysis was seen in only one patient. The clearance of autologous 51 Cr‐labeled RBC was determined in four patients and was slightly enhanced in three and normal in one splenectomized patient. We conclude that the Fc receptor blockade involved in platelet sequestration was not associated with the induction of significant RBC clearance and that a reversible interaction of sensitized RBC with phagocytic cells and/or a low‐grade destruction of these cells might be sufficient for the elevation of circulating platelets in the majority of patients with ITP.
Sensitization rates to food allergens and prevalence of reported and objectively assessed food allergies amongst 15-year olds in UK*1
Authors: B. Pereira, C. Venter, M. Fenn, S. Matthews, J. Grundy, B. Mealy, N. Siddique, S.H. Arshad, T. Dean
Journal: Journal of Allergy and Clinical Immunology (2004)
Issues associated with the design of a national probability sample for human exposure assessment.
Authors: T M Ezzati-Rice, R S Murphy
Journal: Environmental Health Perspectives (1995)

Data obtained from national probability sample surveys provide important information on the prevalence of various health conditions and distributions of physical and biochemical characteristics of the U.S. population. The sample design of a survey specifies how sampling from a designated population over a stated period is to be accomplished. A survey's analytical objectives and interests--in particular subpopulations--affect the sample design strategy. Selected subdomains of the population often must be oversampled so that estimates can be made with acceptable precision. This article addresses sample design considerations for a national probability sample for human tissue monitoring and specimen banking. Among the sampling issues addressed are the oversampling of special populations e.g., minority groups and at-risk groups such as low income or elderly persons; geographic coverage; and sample size considerations. The sample design for a major health survey, the Third National Health and Nutrition Examination Survey (NHANES III), is used to illustrate a complex, multistage probability sample design and to highlight some of the sampling issues discussed in this article.
Cholesterol Lowering With Statin Drugs: Evidence in Women-Reply
Authors: Patricia Hebert
Journal: JAMA (1997)

Dr Wagner notes the paucity of secondary prevention data and virtual lack of primary prevention data concerning cholesterol lowering with statin drugs in women. While awaiting the accumulation of direct data from trials,<sup>1</sup>we believe the overall results rather than sex-specific subgroup analyses provide the most reliable estimates of treatment effects.<sup>2</sup>Further, in the large-scale secondary prevention trials, there do not appear to be qualitative differences in treatment effects between men and women. Thus, it would be unusual to find qualitative differences between men and women in cardiovascular disease benefits in the ongoing primary prevention trials.
Abstract 4693: Inhibition of BET bromodomain targets PTEN positive endometrioid endometrial cancers
Authors: Haifeng Qiu, Amanda Jackson, Joshua Kilgore, Chunxiao Zhou, Victoria Lin Bae-Jump
Journal: Cancer Research (2014)

Abstract Introduction: Endometrioid endometrial cancers (EEC) are commonly characterized by PTEN mutations and loss of function. JQ-1 is a selective small-molecule BET bromodomain inhibitor, and BET inhibition by JQ-1 leads to the downregulation of c-Myc transcription. Thus, JQ-1 functions as a novel c-Myc inhibitor and has been found to potently suppress tumor growth in many human cancers. Given the known interactions between c-Myc and the PI3K/Akt/mTOR pathway, we aim to assess the impact of JQ-1 on human EEC cell lines and further explore the mechanism underlying cellular resistance to JQ-1 treatment. Methods: Six EEC cancer cell lines were used in this study. Cell proliferation was assessed by MTT assay and colony formation assay after exposure to JQ-1. Cell cycle progression was evaluated by flow cytometry. Apoptosis was assessed by Annexin V-FITC assay. Expression of c-Myc, PTEN, phosphorylated-Akt, phosphorylated-S6, cyclins and cyclin-dependent kinases (CDKs) was detected by Western blotting analysis. Up- or down-regulation of PTEN was achieved by stable transfection with pcDNA3.1-PTEN or shRNA-PTEN, respectively. Results: JQ-1 significantly suppressed proliferation in the EEC cell lines that were PTEN positive (IC50=75 nM for HEC-1A, 550 nM for KLE and 1000 nM for ECC-1), but not in those that were PTEN negative (IC50&amp;gt;10000 nM for Ishikawa, AN3CA and RL 95-2). JQ-1 induced G1 cell cycle arrest in the PTEN positive HEC-1A and KLE cell lines, but had minimal effects on cell cycle progression in the PTEN negative Ishikawa and AN3CA cell lines. Western blotting analysis demonstrated that JQ-1 suppressed the expression of c-Myc, cyclins and CDKs. JQ-1 up-regulated PTEN expression and decreased phosphorylation of downstream targets of the PI3K/Akt/mTOR signaling pathway, including Akt and S6. Knock-down of PTEN led to cellular resistance to JQ-1 in the HEC-1A and KLE cells, while over-expression of PTEN sensitized Ishikawa and AN3CA cells to JQ-1 treatment. Conclusions: We find that JQ-1 significantly suppressed cellular proliferation through G1 cell cycle arrest in the EEC cell lines with abundant PTEN expression. Knock-down of PTEN caused cellular resistance while over-expression of PTEN sensitized EEC cells to JQ-1. This evidence suggests that JQ-1 may be a promising targeted therapy for EEC patients with PTEN positive tumors. Note: This abstract was not presented at the meeting. Citation Format: Haifeng Qiu, Amanda Jackson, Joshua Kilgore, Chunxiao Zhou, Victoria Lin Bae-Jump. Inhibition of BET bromodomain targets PTEN positive endometrioid endometrial cancers. [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 4693. doi:10.1158/1538-7445.AM2014-4693
Electrospun Nanofibers‐Mediated On‐Demand Drug Release
Authors: Menglin Chen, Yan‐Fang Li, Flemming Besenbacher
Journal: Advanced Healthcare Materials (2014)

A living system has a complex and accurate regulation system with intelligent sensor‐processor‐effector components to enable the release of vital bioactive substances on demand at a specific site and time. Stimuli‐responsive polymers mimic biological systems in a crude way where an external stimulus results in a change in conformation, solubility, or alternation of the hydrophilic/hydrophobic balance, and consequently release of a bioactive substance. Electrospinning is a straightforward and robust method to produce nanofibers with the potential to incorporate drugs in a simple, rapid, and reproducible process. This feature article emphasizes an emerging area using an electrospinning technique to generate biomimetic nanofibers as drug delivery devices that are responsive to different stimuli, such as temperature, pH, light, and electric/magnetic field for controlled release of therapeutic substances. Although at its infancy, the mimicry of these stimuli‐responsive nanofibers to the function of the living systems includes both the fibrous structural feature and bio‐regulation function as an on demand drug release depot. The electrospun nanofibers with extracellular matrix morphology intrinsically guide cellular drug uptake, which will be highly desired to translate the promise of drug delivery for the clinical success.
Rectal Juvenile Polyp Detected on 99mTc-Pertechnetate Abdominal Scintigraphy (Meckel Scan)
Authors: Cheng Hiang Lee, Edward O’Loughlin, David Ken Vin Chung
Journal: Clinical Nuclear Medicine (2013)

An 8-year-old boy presented with first episode of rectal bleeding. Initial hemoglobin was 9 g/dL. A Meckel scan showed a hyperemic focus in the lower pelvis. Colonoscopy identified a juvenile polyp with dysplasia in the rectosigmoid region. It is important to carefully evaluate the dynamic flow images in the Meckel scan because pathology other than a Meckel diverticulum may be identified.
Mechanism of Nitric Oxide–Induced Vasodilatation
Authors: Richard A. Cohen, Robert M. Weisbrod, Marion Gericke, Mohammad Yaghoubi, Charlene Bierl, Victoria M. Bolotina
Journal: Circulation Research (1999)

Abstract —The precise mechanisms by which nitric oxide (NO) decreases free [Ca 2+ ] i , inhibits Ca 2+ influx, and relaxes vascular smooth muscle are poorly understood. In rabbit and mouse aorta, agonist-induced contractions and increases in [Ca 2+ ] i were resistant to nifedipine, suggesting Ca 2+ entry through non–L-type Ca 2+ channels. Relaxations to NO were inhibited by thapsigargin (TG) or cyclopiazonic acid (CPA) indicating the involvement of sarcoplasmic reticulum ATPase (SERCA). Studies of the effect of NO on [Ca 2+ ] i and the rate of Mn 2+ influx with fura-2 fluorometry in rabbit aortic smooth muscle cells in primary culture were designed to test how SERCA is involved in mediating the response to NO. When cells were stimulated with angiotensin II (AII), NO accelerated the removal of Ca 2+ from the cytoplasm, decreased [Ca 2+ ] i , and inhibited Ca 2+ and Mn 2+ influx. Inhibition of SERCA abolished all the effects of NO. In contrast, inhibition of the Na + /Ca 2+ exchanger or the plasma membrane Ca 2+ ATPase had no influence on the ability of NO to decrease [Ca 2+ ] i . NO maximally decreased [Ca 2+ ] i within 5 s, whereas significant inhibition of AII-induced Ca 2+ and Mn 2+ influx required more than 15 s. The inhibition of cation influx strictly depended on [Ca 2+ ] o and functional SERCA, suggesting that during the delay before NO inhibits Ca 2+ influx, the influx of Ca 2+ and the uptake into intracellular stores are required. In the absence of [Ca 2+ ] o , NO diminished the AII-induced [Ca 2+ ] i transient by a SERCA-dependent mechanism and increased the amount of Ca 2+ in the stores subsequently released by ionomycin. The present study indicates that the initial rapid decrease in [Ca 2+ ] i caused by NO in vascular smooth muscle is accounted for by the uptake of Ca 2+ by SERCA into intracellular stores. It is proposed that the refilling of the stores inhibits store-operated Ca 2+ influx through non–L-type Ca 2+ conducting ion channels and that this maintains the decrease in [Ca 2+ ] i and NO-induced relaxation.
Tumor immunotherapy: inching toward the finish line
Authors: Tyler J. Curiel, David T. Curiel
Journal: Journal of Clinical Investigation (2002)

Despite significant advances in therapy for early-stage cancer, the prognosis for most advanced-stage tumors remains little changed over the past 50 years (1). A vast array of novel strategies has been introduced over this period, many of them building on a recent explosion of insights into tumor immunology. Early attempts at cancer immunotherapy focused on IL-2 or other T cell–activating cytokines that were intended to expand the number or potency of T cells specific for tumor-associated antigens (TAAs). Such activated T cells were expected to infiltrate the tumor and lead to the specific destruction of tumor cells. Although these attempts to boost antitumor immunity have yielded some limited examples of tumor regression, they have failed so far to control advanced-stage disease to a significant extent (2).

Effective T cell activation depends on the presentation of TAAs by antigen-presenting cells (APCs), such as macrophages, fibroblasts, B cells, or dendritic cells (DCs). Of these, only DCs can prime naive T cells, inducing their differentiation into antigen-specific effector cells. This feature, which was recognized early on, could potentially make DCs ideal agents for promoting TAA-specific immunity. Until recently, however, the rarity of these cells and the inability to cultivate them in large numbers hampered progress in this field. The development of techniques by which DCs can be differentiated ex vivo in large numbers revolutionized their study (3) and led to human trials that demonstrated the beneficial effects of TAA-expressing DCs, at least for some tumors (2, 3). The report of Heiser et al. in this issue of the JCI (4) now provides additional encouraging clinical data that confirm the promise of DC-based immunotherapy.
THE LOCALIZATION OF IN VIVO BOUND COMPLEMENT IN TISSUE SECTIONS
Authors: P. J. Lachmann, H. J. Müller-Eberhard, H. G. Kunkel, F. Paronetto
Journal: The Journal of Experimental Medicine (1962)

A technique has been described for the demonstration of a human complement component by an immunofluorescent method. The component detected is ß1C-globulin, a moiety of the third complement component, which has previously been obtained in pure form and to which a specific antiserum has been prepared. It has been shown in a model system that the binding of ß1C-globulin as shown by immunofluorescence is strictly equivalent to complement fixation as assessed by standard serological methods. This technique has been applied to the detection of in vivo bound complement in pathological human tissues. It was found that in vivo complement binding occurs in the lesions of several human diseases, but not elsewhere in the same tissues. In a rather limited survey of diseases that has been carried out, in vivo complement binding was found particularly in systemic L.E., various nephritides, and amyloidosis, as well as in single cases of some other diseases. The spectrum of in vivo complement binding has been compared with that of γ-globulin binding (7S and 19S types) and with the demonstration of in vitro complement fixation and rheumatoid factor fixation. It was distinct from each of these. Rheumatoid factor fixation, detected by anti-19S antiserum showed promise as a method for the detection of antigen-antibody complexes and aggregated γ-globulin in tissue sections. The interpretation of these findings in regard to the nature of the binding sites, and their possible significance in regard to pathogenic mechanisms have been discussed.
Uncommon clinical patterns of Fusarium nail infection: report of three cases
Authors: R. BARAN, A. TOSTI, B.M. PIRACCINI
Journal: British Journal of Dermatology (1997)

Three cases of proximal subungual onychomycosis due to Fusarium oxysporum, including a patient with a fingernail infection, are described. All patients were immunocompetent and presented with acute paronychia associated with proximal or total leukonychia of the affected nails. Nail avulsion followed by topical treatment produced clinical and mycological cure. The literature on Fusarium onychomycosis is discussed. The combination of proximal subungual onychomycosis with subacute or acute paronychia involving fingernails or toenails is highly suggestive of Fusarium sp.
Touching a Cure of an Inveterate Phrensy by the Transfusion of Blood
Authors: Ralph J. Wedgwood, Gretchen R. Riese
Journal: New England Journal of Medicine (1953)

SAMUEL PEPYS1 referred as follows to the work of Drs. Richard Lower and Edmund King, which was presented at Gresham College, where the first attempts at transfusion were performed, and which led to a plot of intrigue, blackmail and possibly murder during this early phase of scientific progress, culminating in the obstruction of further investigation (in this case probably most justifiably) by governmental intervention:November 14, 1666: Tonight there was a pretty experiment of the blood of one dog let out till he died into the body of another on one side. This did give occasion to many pretty wishes, . . .
Evaluation of a diagnostic algorithm for heart disease in neonates.
Authors: R C Franklin, D J Spiegelhalter, F J Macartney, K Bull
Journal: BMJ (1991)

OBJECTIVE--To develop, test, and validate an algorithm for diagnosing disease in neonates during an over the telephone referral to a specialist cardiac centre. DESIGN--A draft algorithm requiring only data available to a referring paediatrician was generated. This was modified in the light of a retrospective review of case records. A questionnaire to elicit all the data required by the algorithm was then generated. There followed a prospective three phase evaluation during consecutive over the telephone referrals. This consisted of (a) a conventional phase with unstructured referral consultations, (b) a phase with referrals structured around the questionnaire but independent of the algorithm, and (c) a validation phase with the algorithm (and its previous errors) available during the referral consultation. SETTING--59 paediatric centres in south east England and a central specialist paediatric cardiology unit. PATIENTS--Consecutive neonates (aged less than 31 days) referred with suspected heart disease. The retrospective review was of records of 174 neonates from 1979. In the prospective evaluation (1987-90) the conventional phase comprised 71 neonates (over 5.5 months), the structured phase 203 neonates (over 14 months), and the validation phase 195 neonates (over 12 months). MAIN OUTCOME MEASURES--Diagnostic accuracy (assigning patients to the correct diagnostic category (out of 27)), of the referring paediatrician, the specialist after the referral consultation, and the algorithm as compared with the definitive diagnosis by echocardiography at the specialist centre, and score for the appropriateness of management in transit. RESULTS--Simply structuring the consultation by questionnaire (that is, proceeding from the conventional phase to the structured phase) improved the diagnostic accuracy of both paediatricians (from 34% (24/71 cases) to 48% (97/203) correct) and specialists (from 54% (38/71 cases) to 64% (130/203) correct). The algorithm (structured phase) would have been even more accurate (78% (158/203 cases); p less than 0.01). Management scores in the structured phase were also better than in the conventional phase (80%(162/203 cases)v 58% (41/71) appropriate; p less than 0.01). Management scores would have improved to 91% appropriate (185/203; p less than 0.001) had the algorithmic diagnoses dictated management. The superiority of the algorithm was maintained but not bettered in the validation phase. CONCLUSIONS--Applying the algorithm should reduce the morbidity and mortality of neonates with critical heart disease by aiding clinicians in therapeutic decisions for in transit care.