tbuckley/cabot-search huggingface dataset:
Negative Feedback Regulation of IFN-γ Pathway by IFN Regulatory Factor 2 in Esophageal Cancers
Authors: Yan Wang, Dongping Liu, Pingping Chen, H. Phillip Koeffler, Xiangjun Tong, Dong Xie
Journal: Cancer Research (2008)

Abstract IFN-γ is an antitumor cytokine that inhibits cell proliferation and induces apoptosis after engagement with the IFN-γ receptors (IFNGR) expressed on target cells, whereas IFN regulatory factor 2 (IRF-2) is able to block the effects of IFN-γ by repressing transcription of IFN-γ–induced genes. Thus far, few studies have explored the influences of IFN-γ on human esophageal cancer cells. In the present study, therefore, we investigated in detail the functions of IFN-γ in esophageal cancer cells. The results in clinical samples of human esophageal cancers showed that the level of IFN-γ was increased in tumor tissues and positively correlated with tumor progression and IRF-2 expression, whereas the level of IFNGR1 was decreased and negatively correlated with tumor progression and IRF-2 expression. Consistently, in vitro experiments showed that low concentration of IFN-γ induced the expression of IRF-2 with potential promotion of cell growth, and moreover, IRF-2 was able to suppress IFNGR1 transcription in human esophageal cancer cells by binding a specific motif in IFNGR1 promoter, which lowered the sensitivity of esophageal cancer cells to IFN-γ. Taken together, our results disclosed a new IRF-2–mediated inhibitory mechanism for IFN-γ–induced pathway in esophageal cancer cells: IFN-γ induced IRF-2 up-regulation, then up-regulated IRF-2 decreased endogenous IFNGR1 level, and finally, the loss of IFNGR1 turned to enhance the resistance of esophageal cancer cells to IFN-γ. Accordingly, the results implied that IRF-2 might act as a mediator for the functions of IFN-γ and IFNGR1 in human esophageal cancers. [Cancer Res 2008;68(4):1136–43]
PERSISTENT HYALOID ARTERY
Authors: L. M. BOWES
Journal: JAMA (1913)

There is no doubt that many cases of persistent hyaloid artery are unrecognized, and it is my object, as a general practitioner, to report a case as an aid to the pediatrician or the general practitioner who first sees one of these cases and may be at a loss to account for the complaint of a shadow or dark object floating before the eye, as well as the persistent headache or ocular pain which may accompany this condition. Or, as in the case which I shall report, a young child may shake its head to get the loose end of a persistent hyaloid artery out of the line of vision. There is usually defective vision, although Krauss<sup>1</sup>found the vision normal in both eyes of a colored woman aged 41, who complained of a dark object floating before her eyes, which she had noticed for three weeks. She also
Cocaine, Alcohol Mix in Body to Form Even Longer Lasting, More Lethal Drug
Authors: Teri Randall
Journal: JAMA (1992)

RESEARCHERS have demonstrated probably for the first time that, in the presence of two drugs, the body creates a third. The discovery is not just an interesting pharmacologic phenomenon, however, but a serious health concern because of the two drugs involved—cocaine and alcohol. And for the 12 million people who combine these drugs every year, it is sobering news. In the presence of cocaine and ethanol, the liver metabolizes cocaine to its ethyl homologue, called cocaethylene. That much has been known since 1978. But what wasn't known is that cocaethylene is a neurologically active compound that provides the same feelings of euphoria and well-being as cocaine, only more intensely and for longer periods. It is probably more addictive than the parent drug, and it is certainly more lethal. <h3>Dopamine Mediates the Hook</h3> Previous studies have shown that cocaine acts on the central nervous system (CNS) by blocking the reuptake of
An Address ON SOME POINTS CONCERNING TUBERCLE, SYPHILIS AND MALIGNANT DISEASE
Authors: R. Morison
Journal: BMJ (1910)

GENTLBMEN,-I highly appreciate the honour of being asked to address you, and have selected for my subject three of the most common and most interesting of surgical diseses-tubercle, syphilis, and malignant disease.It hag been helpful to me, and I trust it may be to you, to consider them together.For two of them-syphilis and tubercle-the responsible organism has been discovered.It is still being searehed for in respect to cancer and sarcoma.All of these diseases commence locally, and spread
Interarterial Coronary Anastomoses
Authors: BERTRAM PITT
Journal: Circulation (1959)

It is generally recognized that interarterial coronary anastomoses of functionally significant size occur with great frequency in the presence of occlusive coronary artery disease and in other conditions such as anemia and cardiac hypertrophy in which myocardial anoxia may be present. Disagreement has been expressed by some investigators regarding the incidence of these anastomoses in normal and abnormal hearts. The problem has therefore been reinvestigated by means of a technic of infusion of saline solution and injection of wax spheres of known size. The results of these observations in 75 hearts are presented and their significance is discussed.
Cardiac Arrhythmias Simulated by Concealed Bundle of His Extrasystoles in the Dog
Authors: ANTHONY N. DAMATO, SUN H. LAU, GUSTAVUS BOBB
Journal: Circulation Research (1971)

In 10 open-chest intact dog hearts, multiple close bipolar electrograms were obtained from various regions of both atria and the bundle of His. The bundle of His was also prematurely stimulated at varying coupling intervals following a sinus beat. At short coupling intervals, the bundle of His stimulus failed to propagate antegradely (no ventricular response) but did propagate retrogradely. Coupled bundle of His stimuli retrogradely concealed within the A-V node caused the next sinus impulse to be delayed or blocked. Types I and II second degree A-V block, 2:1 A-V block, and alternation of the P-R interval were simulated. An atrial (nonconducted) bigeminal rhythm was simulated when the bundle of His stimuli completely traversed the A-V node and completely (inverted P waves) or partially (fusion P waves) depolarized the atria.
The Physician's Role in Preventing Nuclear War
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1986)

IN this issue we publish a Special Report entitled "New Perspectives on the Medical Consequences of Nuclear War." 1 This document, compiled by Dr. Alexander Leaf, is based on information presented last year at an international symposium sponsored by the Institute of Medicine of the National Academy of Sciences and now available in an important book just released.2 It also reflects material derived from a recent major study sponsored by the International Council of Scientific Unions.3 , 4 Leaf's article deals mainly with new information about the probable numbers of immediate casualties from fire, blast, and radiation; the likely impairment of immune function . . .
Read It Again: It's Good for You
Authors: Germaine Roman
Journal: JAMA (1985)

Most of you believe that a scientific article should be published<i>only once, in one journal</i>. You are, in fact, the self-righteous majority who tries to stifle repetitive publication. The free-thinking individuals who reject such arbitrary rules and manage to break them, in valiant defiance of the copyright law, are a small, scattered, and unorganized group, until now too weak to defend their position publicly. In all fairness, repetitive publication deserves a hearing. Here are my arguments in favor of it. <h3>Wider Dissemination of Information.—</h3> This is a fairly obvious advantage. An article appearing in multiple journals aimed at the same audience is less likely to be missed by those cursory readers and hasty scanners out there. The author of a multiply published article will be able to have the following dialogue with his or her colleagues: "Have you read my article?" "No, where?" "Everywhere! Don't you read<i>anything</i>?" <h3>Repetition</h3>
Understanding and limiting observer variability: Lessons from liver scans
Authors: Ralph I. Horwitz, Donald R. Bordley
Journal: Hepatology (1987)

Two specialists in nuclear medicine and two trainees independently read 106 liver scans for abnormalities suggestive of metastases. The four observers made a positive diagnosis with a significantly different frequency. The overall agreement between pairs of observers was 0.83-0.87. After adjusting for the expected chance agreement, K -values between 0.66 and 0.74 were obtained. No difference was found in the level of agreement between the two specialists or between the two trainees. After a consensus conference where the observers tried to unify their diagnostic interpretation, another 106 scans were read for abnormalities suggestive of metastases. The conference did not increase the level of agreement. Scintigraphic lesions that especially imply a risk of disagreement are pointed out.
Measurement of intraepithelial lymphocytes.
Authors: R Whitehead
Journal: Gut (1986)

Penile ulceration in Crohn's disease SIR,-We read with interest the well documented cases of penile ulceration by Slaney et al (Gut 1986; 27: 329).We wish to describe a case of pyoderma gangrenosum affecting the penis in a patient with Crohn's disease, which had certain similarities.A 46 year old man presented with a few months history of bloody diarrhoea.A barium enema showed characteristic features of Crohn's disease affecting the transverse and descending colon with skip lesions.A small bowel enema was normal.He was treated with prednisolone and sulphasalazine and made a good recovery.Six months later he developed a discharging punched out ulcer on the skin in the interscapular area.The ulcer had typical features of a pyoderma gangrenosum which was confirmed by histology and responded to a local injection of Triamcinolone.At the same time he developed a rapidly enlarging tender nodular lesion on the dorsum of his penis which was excised.Histology showed granulation tissue and the excision resulted in a large ulcer similar to that shown in Fig. 3 of the article by Slaney et al.There was no serological or cytological evidence for a sexually transmitted di- sease.As the ulcer was discharging seropurulent material, was tender and unresponsive to local antibiotics and topical steroids, a six weeks course of oral prednisolone was given.This resulted in a complete healing of the ulcer.Two months later, however, he developed another nodular lesion at the junction of the glans and the shaft of the penis which was also excised.Histology showed typical features of pyoderma gangrenosum.The excision resulted in an ulcer which once again was refractory to topical treatment.In addition, he developed an indurated area 1 cm distal to the ulcer.These lesions failed to heal over the next four months in spite of treatment with oral prednisolone, supplemented later with azathioprine, but healed completely within six weeks of the injection of 2 mg Triamcinolone between the two lesions.During this period, his colitis was in remission.Eighteen months later he remains well and has had no further recurrence of his penile lesions.Our patient shows some differences from the two reported by Slaney et al, although the clinical presentation was similar to that of case 2. Firstly, the penile lesion was a pyoderma gangrenosum rather than an epithelioid granuloma.Secondly, the ulcer did not respond to topical steroids but initially healed with oral steroids and a recurrence healed only after local injection of a corticosteroid drug.As
The tyranny of power: is there a better way to calculate sample size?
Authors: J. M. Bland
Journal: BMJ (2009)

Summary: We report two patients with surgically proved mucoceles involving the anterior clinoid process. One patient had a mucocele of an Onodi cell and the other had a mucocele isolated to the anterior clinoid process. The MR signal was increased on both T1- and T2-weighted images in the first patient but was isointense on both sequences in the second patient, a finding that resulted in misdiagnosis. The developmental and anatomic features, as well as the diagnostic pitfalls, are discussed.
Normal serum cholesterol values. Percentile ranking in a middle-class pediatric population
Authors: G. Friedman
Journal: JAMA (1973)

We determined the serum cholesterol values of 2,033 normal children, ages 2 weeks to 19 years. A test that could be performed in a physician's office was standardized and utilized. It was found that the serum cholesterol values were age-dependent. Analysis of the serum cholesterol values in the various age groups revealed that they were not statistically normally distributed. For this reason, a nomogram similar to the familiar height and weight charts for children was constructed. The nomogram permits the physician to rank a given patient with other children of his age, and to follow the changes in serum cholesterol values in a given patient as he grows older.
Acute and long-term thromboembolic events in patients with atrial tachyarrhythmias: Comparison between atrial fibrillation, atrial flutter plus atrial fibrillation, and pure atrial flutter
Authors: Karlheinz Seidl, Margit Vater, Monika Rameken, Axel Droegemueller, Andreas Brandt, Jochen Senges
Journal: Journal of the American College of Cardiology (2003)
Utility of microdissection and polymerase chain reaction for the detection of immunoglobulin gene rearrangement and translocation in primary intraocular lymphoma
Authors: De Fen Shen, Zhengping Zhuang, Phuc LeHoang, Roland Böni, Sherman Zheng, Robert B Nussenblatt, Chi-Chao Chan
Journal: Ophthalmology (1998)

Primary intraocular lymphoma, a non-Hodgkin's lymphoma, is a primary central nervous system lymphoma (PCNSL). Diagnosis is usually made by identifying malignant, large B lymphocytes in the vitreous, eye, brain, and cerebral spinal fluid; however, these cells are few, friable, and difficult to recognize. Recently, clonal heavy chain immunoglobulin (IgH) gene rearrangement and bcl-2 gene translocation have been reported in systemic B-cell lymphoma and are used for the detection of malignant cells and in making a diagnosis. The authors investigated the molecular changes in three eyes and a chorioretinal biopsy specimen of four patients with PCNSL.Human tissue study.Five ocular specimens of PCNSL were collected.The first patient had a diagnostic enucleation of the left eye. The second patient underwent diagnostic chorioretinal biopsy. In the third case, a pair of autopsied eyes with reactive lymphoplasmacytic infiltrates of a patient with acquired immune deficiency syndrome (AIDS) were studied. In the fourth case, an enucleated eye of a patient with AIDS-associated lymphoma was sampled.The bcl-2 and IgH genes of the lymphoma cells from routine, paraffin-embedded, formaldehyde-fixed, or frozen histologic tissue sections were analyzed using microdissection and polymerase chain reaction (PCR) technique.Lymphoma cells obtained from the above four cases showed IgH rearrangement gene in the third framework of the VH region. Bcl-2-associated translocation also was detected in three cases (cases 1, 2, and 4).Rearrangement of the IgH gene can serve as a molecular marker for PCNSL. Microdissection allows for procurement and analysis of specific, selected, minute cell populations that are obtained from histologic sections of the complex, heterogeneous tissue. Translocation of IgH and bcl-2, the apoptotic "survival" signal and proto-oncogene, could contribute to the pathogenesis of PCNSL. The combination of microdissection and PCR is a powerful tool for studies of small lesions and cell populations and for understanding disease mechanisms.
Risk estimation for badge-monitored radiation workers.
Authors: A Stewart
Journal: Environmental Health Perspectives (1997)

In estimating the cancer mortality risk for radiation workers it is conventional to use data obtained from the populations exposed to radiation as a result of the atomic bomb blast in Hiroshima and Nagasaki. This A-bomb experience resulted in relatively high doses of radiation and short periods of exposure. The availability of systematic analyses of the mortality of workers at the Hanford plant (Washington state) provides a more realistic basis for individual risk estimates. We present the data for three functions that in combination provide useful guidelines for occupational cancer mortality risk. These functions are a relationship between age at exposure, latency between exposure and death, and a dose-response function. Although other estimates of such functions are possible using different populations and assumptions, we offer these functions as guidelines for individual cancer risk evaluation based on our analyses of the Hanford data.
An Essay on Administration
Authors: WILLIAM G. REESE
Journal: American Journal of Psychiatry (1972)

A reasonably sophisticated knowledge of administrative theory and practice is important to psychiatrists in their clinical and educational activities. By virtue of their skills and attitudes, psychiatrists have particular administrative capacities and vulnerabilities. A useful body of administrative knowledge is readily accessible to psychiatrists and should be available to psychiatric residents. The author presents some samples of this knowledge, which includes empirically derived principles and partially tested practices. These, in turn, have generated conceptually useful theories that warrant further testing.
Monitoring Warfarin Therapy in Patients with Lupus Anticoagulants
Authors: Stephan Moll
Journal: Annals of Internal Medicine (1997)

Background: Recommended therapeutic international normalized ratios (INRs) for oral anticoagulation in patients with lupus anticoagulants who sustain a thromboembolic event are controversial. Patients with lupus anticoagulants often have a prolonged prothrombin time, which may complicate management of anticoagulant therapy. Objectives: To determine the validity of the INR as a monitor for warfarin therapy in patients with lupus anticoagulants and to investigate alternate approaches to monitoring warfarin therapy in these patients. Design: Prospective case series. Setting: Tertiary care hospital. Patients: 34 patients with lupus anticoagulants. Measurements: Prothrombin times were determined by using several thromboplastins, and INRs were calculated for the patients receiving warfarin. Factor II levels, chromogenic factor X levels, and prothrombin-proconvertin times were determined for patients receiving warfarin. Results: For patients with lupus anticoagulants who were not receiving warfarin, prothrombin times were often elevated and varied significantly with different thromboplastins. Individual thromboplastins differed in sensitivity to the presence of a lupus anticoagulant. For patients receiving warfarin, INRs obtained by using different thromboplastins greatly varied and often overestimated the extent of anticoagulation. Chromogenic factor X levels and prothrombin-proconvertin times correlated well with each other and with established therapeutic ranges. Conclusions: Lupus anticoagulants can influence prothrombin times and lead to INRs that do not accurately reflect the true level of anticoagulation. Use of the INR to standardize prothrombin times is invalid for some patients with lupus anticoagulants. To prevent supratherapeutic or subtherapeutic anticoagulation, these patients must be individually monitored with a test that is insensitive to lupus anticoagulants.
Adenosine augmentation ameliorates psychotic and cognitive endophenotypes of schizophrenia
Authors: Hai-Ying Shen, Philipp Singer, Nikki Lytle, Catherine J. Wei, Jing-Quan Lan, Rebecca L. Williams-Karnesky, Jiang-Fan Chen, Benjamin K. Yee, Detlev Boison
Journal: Journal of Clinical Investigation (2012)

An emerging theory of schizophrenia postulates that hypofunction of adenosine signaling may contribute to its pathophysiology. This study was designed to test the "adenosine hypothesis" of schizophrenia and to evaluate focal adenosine-based strategies for therapy. We found that augmentation of adenosine by pharmacologic inhibition of adenosine kinase (ADK), the key enzyme of adenosine clearance, exerted antipsychotic-like activity in mice. Further, overexpression of ADK in transgenic mice was associated with attentional impairments linked to schizophrenia. We observed that the striatal adenosine A2A receptor links adenosine tone and psychomotor response to amphetamine, an indicator of dopaminergic signaling. Finally, intrastriatal implants of engineered adenosine-releasing cells restored the locomotor response to amphetamine in mice overexpressing ADK, whereas the same grafts placed proximal to the hippocampus of transgenic mice reversed their working memory deficit. This functional double dissociation between striatal and hippocampal adenosine demonstrated in Adk transgenic mice highlights the independent contributions of these two interconnected brain regions in the pathophysiology of schizophrenia and thus provides the rationale for developing local adenosine augmentation therapies for the treatment of schizophrenia.
Local IL-21 Promotes the Therapeutic Activity of Effector T cells by Decreasing Regulatory T Cells Within the Tumor Microenvironment
Authors: Seunghee Kim-Schulze, Hong Sung Kim, Qing Fan, Dae Won Kim, Howard L Kaufman
Journal: Molecular Therapy (2008)

The eradication of tumors by the immune system depends on the generation of antigen-specific T cells which can migrate to sites of tumor growth and maintain their effector functions despite local tumor-derived T-cell inhibitory factors. Interleukin-21 (IL-21) is an IL-2-related cytokine that has shown limited evidence of antitumor activity in murine models and early phase clinical trials. Effect of local IL-21 on T-cell responses within the tumor microenvironment, however, has not been extensively evaluated. Thus, we developed a stably transfected IL-21-secreting B16 melanoma cell line to test the effects of local IL-21 on endogenous and adoptively transferred T-cell responses. Tumors expressing IL-21 exhibited delayed growth in vivo, which was associated with an increase in activated systemic effector and memory CD8(+) T-cell responses. Local IL-21 also enhanced the therapeutic effects of adoptively transferred gp100-specific T cells and was synergistic with IL-2. The effect was also associated with an increased proliferation of local CD8(+) T cells and decreased accumulation of regulatory CD4(+)FOXP3(+) T cells within the tumor microenvironment. These data suggest that local IL-21 enhances endogenous and adoptively transferred T-cell immunity through increased effector CD8(+) T cells and decreased CD4(+) regulatory T cells in the tumor microenvironment.
Fatty Change in the Myocardium of the Newborn
Authors: J. M. Scott
Journal: BMJ (1961)

PROPATYLNITRATE MEDICALJORNALIt appears that propatylnitrate is a potent drug for the relief of acute attacks of angina pectoris but is of little or no value in prophylaxis.In our opinion there is as yet no drug which can be relied upon to abolish or diminish the frequency of attacks of angina pectoris. ConclusionIn the doses used sublingually propatylnitrate and PETN did not differ significantly from a placebo in abolishing or diminishing the frequency of attacks of angina pectoris.We thank Dr.