tbuckley/cabot-search huggingface dataset:
Analysis of antigenic determinants shared by two different allergens recognized by human T cells: house dust mite (<i>Dermatophagoides pteronyssinus</i>) and chironomid midge (<i>Chironomus yoshimatsui</i>)
Authors: T. Nagano, N. Ohta, M. Okano, T. Ono, Y. Masuda
Journal: Allergy (1992)

To analyse the cross‐reactivity of T‐cell‐mediated immunity between Dermatophagoides pteronyssinus (Dp) and Chironomus yoshimatsui (Cy), the most common allergens in Japan, we established antigen‐specific human T‐cell lines and clones. Some but not all of the Cy‐induced T‐cell lines showed a significant proliferative response not only to Cy, but also to Dp. No T‐cell line responded to other unrelated antigens. When we stimulated the Dp‐induced T‐cell clones with Cy, 3 of the 40 clones (7.5%) showed a significant proliferation, and 2 of the 3 clones produced interleukin‐4 and interferon‐γ, indicating their helper function, Cross‐reactivity was diminished significantly after the absorption of Dp antigen in an anti‐Cy affinity column. The cross‐reactive epitopes were thought to be expressed on the Dp molecule of 45–53 kD, The presence of helper T cells reactive to both allergens suggests a possibility that this cross‐reactivity might be involved in part in the high incidence of allergy to the 2 major allergens.
Eleven Worthy Aims for Clinical Leadership of Health System Reform
Authors: Donald M. Berwick
Journal: JAMA (1994)

Clinicians ought to be playing a central role in making the changes in the health care system that will allow the system to offer better outcomes, greater ease of use, lower cost, and more social justice in health status. Instead, most of the proposed changes that are today called "health care reform" are actually changes in the surroundings of care rather than changes in the care itself. Clinicians have an opportunity to exercise leadership for the improvement of care, but they must first agree to address the aims of reform and to adopt an agenda of specific changes in their own work that are likely to meet the social needs driving the reform movement. Health services research offers a sound scientific basis for identifying promising improvement aims for clinician-led reform. Eleven plausible aims are these: (1) reducing inappropriate surgery, hospital admissions, and diagnostic tests; (2) reducing key underlying root causes of illness (especially smoking, handgun violence, preventable childhood injuries, and alcohol and cocaine abuse); (3) reducing cesarean section rates to pre-1980 levels; (4) reducing the use of unwanted medical procedures at the end of life; (5) simplifying pharmaceutical use, especially for antibiotics and medication of the elderly; (6) increasing active patient participation in therapeutic decision making; (7) decreasing waiting times in health care settings; (8) reducing inventory levels in health care organizations; (9) recording only useful information only once; (10) consolidating and reducing the total supply of high-technology medical and surgical care; and (11) reducing the racial gap in infant mortality and low birth weight. Health care professions and their professional organizations in concert should embrace these 11 aims, establish measurements of progress toward them, and commit to continuous and fundamental changes in their pursuit. (<i>JAMA</i>. 1994;272:797-802)
Cancer of the Cervix Stage II
Authors: Philip Rubin
Journal: JAMA (1965)

ABSTRACT Although radiation therapy is generally considered the procedure of choice in treating invasive carcinoma of limited extent, the renaissance of radical surgical procedures in experienced hands has yielded high cure rates. Rather than regard these procedures as competitive, an effort is being made in a number of centers to use the surgical and radiotherapeutic modes in a complimentary fashion and to thereby provide a treatment specifically suited to each patient. To this end, a number of tests are being developed to predict the radiosensitivity and radiocurability of an individual case prior to or during irradiation, so that surgical intervention may permit successful salvage of a cancer likely to persist or recur because of radioresistance.One of the commonly stated concepts is that anaplastic tumors are radiosensitive and well-differentiated carcinomas are radioresistant. Although support for this view can be found in Martzloff's1 and Novak's2 studies, which suggest that differentiated
Oncogenes: Implications for the Diagnosis and Treatment of Cancer
Authors: MARTIN J. CLINE
Journal: Annals of Internal Medicine (1984)

Cellular oncogenes comprise a small family of genes, highly conserved throughout vertebrate evolution, that code for proteins with diverse functions including DNA binding, protein kinase, and cellular growth factor activities. Cellular oncogenes are important in certain aspects of the proliferation and differentiation of normal cells. Under some circumstances these genes may also induce malignant transformation of normal cells. Various mechanisms may underlie their involvement in carcinogenesis. Incorporation of all, or part of, cellular oncogenes into RNA tumor viruses, mutations in gene structure, or translocation of cellular oncogenes from one chromosome to another may all be associated with the induction of malignant change in cells. In some of these situations altered oncogene products are made. Knowledge about the biology of oncogenes may lead to improved techniques for cancer detection and perhaps new approaches to cancer treatment.
Bad medicine or bad mouthing?
Authors: I. M. Anderson
Journal: BMJ (2011)

Spence’s column about bipolar II disorder is disappointing and disconcerting.1 He launches an uninformed attack on psychiatry with selective quoting of evidence, which raises some concerns for the patients he sees with mental health problems.

This is a shame because implicit in his article are issues that we as a profession struggle with, and which are not confined to psychiatry. The first is how to deal with a …
Long-chain acylcarnitines mediate the hypoxia-induced increase in alpha 1-adrenergic receptors on adult canine myocytes.
Authors: G P Heathers, K A Yamada, E M Kanter, P B Corr
Journal: Circulation Research (1987)

To elucidate the mechanisms responsible for the increase in alpha 1-adrenergic receptors during ischemia in vivo, we developed a procedure for measuring alpha 1-adrenergic receptors in isolated, calcium-tolerant adult canine myocytes. Specific [3H]prazosin binding was rapid, saturable, reversible, and demonstrated the expected order of potency and stereospecificity for the alpha 1-adrenergic receptor. Myocytes exposed to 30 minutes of hypoxia at 25 degrees C or only 10 minutes at 37 degrees C exhibited a twofold to threefold increase in the number of alpha 1-adrenergic receptors with no significant change in receptor affinity. This hypoxia-induced increase in receptor number was reversible by 10 minutes of reoxygenation at 37 degrees C. In contrast, more prolonged hypoxia of 80 minutes or hypotonic shock actually decreased receptor number below normoxic, control values. The concentration of long-chain acylcarnitines in myocytes also increased threefold on exposure to 30 minutes of hypoxia. Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA, 10 microM), a potent inhibitor of carnitine acyltransferase I, not only abolished the accumulation of long-chain acylcarnitines but also the increase in alpha 1-adrenergic receptor number induced by 30 minutes of hypoxia. Likewise, incubation of normoxic cells with exogenous palmitoyl carnitine (1 microM) for 10 minutes also increased alpha 1-adrenergic receptor number in the presence or absence of POCA. Thus, hypoxia results in an increase in alpha 1-adrenergic receptors associated with an increase in endogenous long-chain acylcarnitines. Furthermore, inhibition of carnitine acyltransferase I prevents not only the sarcolemmal accumulation of long-chain acylcarnitines but also the exposure of the alpha 1-adrenergic receptor, indicating that accumulation of endogenous long-chain acylcarnitines is critical to the hypoxia-induced increase in alpha 1-adrenergic receptors on adult myocytes.
Ineffectiveness of Chlordiazepoxide Hydrochloride in Epilepsy
Authors: Samuel Livingston, Lydia Pauli, John B. Murphy
Journal: JAMA (1961)

Chlordiazepoxide, a widely used antianxiety drug, has previously been reported to be effective in the treatment of various types of epilepsy. While the manufacturer does not recommend its use for this indication at this time, except by experienced investigators, the publication of 2 favorable reports on its effectiveness in convulsive disorders warrants publication of the following negative report to alert physicians to the difficulties one may encounter in the evaluation of drugs in this difficult clinical problem.
Hydroxyl radical mediates the endothelium-dependent relaxation produced by bradykinin in mouse cerebral arterioles.
Authors: W I Rosenblum
Journal: Circulation Research (1987)

Bradykinin relaxes arterioles on the brain's surface. This response is endothelium-dependent. The data presented here confirm the hypothesis that hydroxyl free radical mediates this response and may be the endothelium-dependent relaxing factor for bradykinin in this microvascular bed. The response to a locally applied bolus of bradykinin (80 micrograms/ml) was monitored by intravital TV microscopy. The response was significantly inhibited or totally blocked by the presence of superoxide dismutase 60 U/ml, catalase 46 U/ml, or deferoxamine 0.1 or 0.2 mM. The superoxide dismutase scavenges superoxide radical, which is known to enter the subarachnoid space as a consequence of cyclooxygenase activation. Cyclooxygenase is activated by bradykinin. The superoxide can form H2O2, scavenged by catalase, and the two together generate hydroxyl. The formation of hydroxyl radical is catalyzed by iron. Deferoxamine 0.1 mM scavenges the iron, blocking the generation of hydroxyl. Deferoxamine 0.2 mM also directly scavenges the hydroxyl. None of the pharmacologic probes had an effect on arteriolar diameter when locally applied without bradykinin. Since the dilation produced by bradykinin was inhibited or totally blocked by probes that prevented hydroxyl formation or directly scavenged hydroxyl radical, that radical is either an essential mediator of the arteriolar relaxation, or is the endothelium-dependent relaxing factor for bradykinin in pial arterioles.
Quality of Life, Burnout, Educational Debt, and Medical Knowledge Among Internal Medicine Residents
Authors: Colin P. West, Tait D. Shanafelt, Joseph C. Kolars
Journal: JAMA (2011)

Physician distress is common and has been associated with negative effects on patient care. However, factors associated with resident distress and well-being have not been well described at a national level.To measure well-being in a national sample of internal medicine residents and to evaluate relationships with demographics, educational debt, and medical knowledge.Study of internal medicine residents using data collected on 2008 and 2009 Internal Medicine In-Training Examination (IM-ITE) scores and the 2008 IM-ITE survey. Participants were 16,394 residents, representing 74.1% of all eligible US internal medicine residents in the 2008-2009 academic year. This total included 7743 US medical graduates and 8571 international medical graduates.Quality of life (QOL) and symptoms of burnout were assessed, as were year of training, sex, medical school location, educational debt, and IM-ITE score reported as percentage of correct responses.Quality of life was rated "as bad as it can be" or "somewhat bad" by 2402 of 16,187 responding residents (14.8%). Overall burnout and high levels of emotional exhaustion and depersonalization were reported by 8343 of 16,192 (51.5%), 7394 of 16,154 (45.8%), and 4541 of 15,737 (28.9%) responding residents, respectively. In multivariable models, burnout was less common among international medical graduates than among US medical graduates (45.1% vs 58.7%; odds ratio, 0.70 [99% CI, 0.63-0.77]; P < .001). Greater educational debt was associated with the presence of at least 1 symptom of burnout (61.5% vs 43.7%; odds ratio, 1.72 [99% CI, 1.49-1.99]; P < .001 for debt >$200,000 relative to no debt). Residents reporting QOL "as bad as it can be" and emotional exhaustion symptoms daily had mean IM-ITE scores 2.7 points (99% CI, 1.2-4.3; P < .001) and 4.2 points (99% CI, 2.5-5.9; P < .001) lower than those with QOL "as good as it can be" and no emotional exhaustion symptoms, respectively. Residents reporting debt greater than $200,000 had mean IM-ITE scores 5.0 points (99% CI, 4.4-5.6; P < .001) lower than those with no debt. These differences were similar in magnitude to the 4.1-point (99% CI, 3.9-4.3) and 2.6-point (99% CI, 2.4-2.8) mean differences associated with progressing from first to second and second to third years of training, respectively.In this national study of internal medicine residents, suboptimal QOL and symptoms of burnout were common. Symptoms of burnout were associated with higher debt and were less frequent among international medical graduates. Low QOL, emotional exhaustion, and educational debt were associated with lower IM-ITE scores.
Nocturnal Angina Pectoris
Authors: Michael Andrisani
Journal: JAMA (1969)

<h3>To the Editor:—</h3> A major precipitating factor in nocturnal angina pectoris has not been stressed. I am impressed that angina occurring during sleep is the result of the tremendous physiologic response to dreams. Several authors have noted increases and irregularity of heart rate, respiration, and arterial pressure occurring in nearly all instances of D-sleep (sleep associated with dreaming).<sup>1,2</sup> Shifts in the blood pressure might be dangerous to a cardiac patient, and as early as 1921, it had been suggested that sudden death during sleep of patients with heart disease was probably caused by blood pressure changes associated with dreaming.<sup>3</sup> I have recently had occasion to see a 68-year-old woman with a two-month history of nocturnal angina. The patient had already been receiving long-acting nitrates, she eats lightly, and has no upper- gastrointestinal tract problems. The patient awakens with chest pain, walks around the room, and has dreamed of
THE EFFECT OF TOPICAL CYPROTERONE ACETATE ON SEBUM SECRETION IN PATIENTS WITH ACNE
Authors: W. J. CUNLIFFE, SAM SHUSTER, A. J. CASSELS SMITH
Journal: British Journal of Dermatology (1969)

Journal Article THE EFFECT OF TOPICAL CYPROTERONE ACETATE ON SEBUM SECRETION IN PATIENTS WITH ACNE Get access W. J. CUNLIFFE, W. J. CUNLIFFE University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne and Department of Pathology, Newcastle General Hospital, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar SAM SHUSTER, SAM SHUSTER University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne and Department of Pathology, Newcastle General Hospital, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar A. J. CASSELS SMITH A. J. CASSELS SMITH University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne and Department of Pathology, Newcastle General Hospital, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 3, 1 March 1969, Pages 200–201, https://doi.org/10.1111/j.1365-2133.1969.tb16007.x Published: 01 March 1969 Article history Accepted: 14 August 1968 Published: 01 March 1969
Penny Wise, Pound Foolish? Coverage Limits on Immunosuppression after Kidney Transplantation
Authors: John S. Gill, Marcello Tonelli
Journal: New England Journal of Medicine (2012)

Since U.S. kidney-transplant recipients don't benefit from a coherent funding policy for immunosuppressive drugs, thousands of them are at risk for allograft failure and premature death. Ensuring lifetime access to these medications would save lives and money.
"SHALL THE PUBLIC TAKE FULL RESPONSIBILITY FOR SMALLPOX?"
Authors: Emanuel Stuver
Journal: JAMA (1924)

<h3>To the Editor:</h3> —Referring to Dr. Gage's letter on this subject (The Journal, September 20), I recall the spirited discussion of smallpox at the Association meeting in Los Angeles in June, 1911. In discussing the reports on smallpox by Dr. Spalding and Dr. Bracken which, with discussions, were published inThe Journal, Oct. 14, 1911, I said in part: I am highly pleased that so distinguished an authority as Dr. Bracken takes the stand he does on the question of quarantine.... What does quarantine do? It gives us a wall behind which the antivaccinationists can hide; they cry to the public: "Isolate cases of smallpox," and they can shoot into the scientific world with the material they gather from all sources and keep up a battle of that sort; whereas, if we turned our smallpox patient loose, we would see those people taking to the woods. They would get vaccinated,
Esophageal obstruction by solidification of the enteral feed: a complication to be prevented
Authors: P. P. García-Luna, E. García, J. L. Pereira, M. Garrido, J. Parejo, V. Migens, P. Serrano, H. Romero, T. Gómez-Cía, F. Murillo
Journal: Intensive Care Medicine (1997)
A Novel Small Molecule Inhibitor of Signal Transducers and Activators of Transcription 3 Reverses Immune Tolerance in Malignant Glioma Patients
Authors: S. Farzana Hussain, Ling-Yuan Kong, Justin Jordan, Charles Conrad, Timothy Madden, Isabella Fokt, Waldemar Priebe, Amy B. Heimberger
Journal: Cancer Research (2007)

Overcoming the profound immunosuppression in patients with solid cancers has impeded efficacious immunotherapy. Signal transducers and activators of transcription 3 (STAT3) has recently emerged as a potential target for effective immunotherapy, and in this study, we describe a novel small molecule inhibitor of STAT3 that can penetrate the central nervous system (CNS) in mice and in physiologically relevant doses in vitro and reverse tolerance in immune cells isolated from glioblastoma multiforme (GBM) patients. Specifically, it induces the expression of costimulatory molecules on peripheral macrophages and tumor-infiltrating microglia, stimulates the production of the immune-stimulatory cytokines interleukin 2 (IL-2), IL-4, IL-12, and IL-15, and induces proliferation of effector T cells from GBM patients that are refractory to CD3 stimulation. We show that the functional enhancement of immune responses after STAT3 inhibition is accompanied by up-regulation of several key intracellular signaling molecules that critically regulate T-cell and monocyte activation. Specifically, the phosphorylation of Syk (Tyr352) in monocytes and ZAP-70 (Tyr319) in T cells are enhanced by the STAT-3 inhibitor in marked contrast to toll-like receptor and T-cell receptor agonists, respectively. This novel small molecule STAT3 inhibitor has tremendous potential for clinical applications with its penetration into the CNS, easy parental administration, direct tumor cytotoxicity, and potent immune adjuvant responses in immunosuppressed cancer patients.
Sarcoma of the Uterus
Authors: Thomas Perry
Journal: New England Journal of Medicine (1948)

ALTHOUGH sarcomas of the uterus are rare in comparison with the carcinomas of that organ, certain features of their histogenesis, pathology and clinical course make them an interesting group. Two recent cases, a sarcoma botroides and a late metastasizing leiomyosarcoma, prompted a review of the 18 cases of sarcoma of the uterus seen at the Rhode Island Hospital in the past eighteen years. Special attention has been paid to the pathology of these cases with a view to determining their probable origins and the relation of cytologic characteristics to prognosis. Observations have also been made on the clinical characteristics of . . .
Proximal Tubule Potential Difference. DEPENDENCE ON GLUCOSE, HCO3, AND AMINO ACIDS
Authors: Juha P. Kokko
Journal: Journal of Clinical Investigation (1973)

The effect of various intraluminal substrates on the magnitude of the transepithelial potential difference (PD) across the proximal convoluted tubule (PCT) of the mammalian kidney was investigated in two ways. First, the transepithelial PD was measured before and after the removal of glucose, bicarbonate, and alanine from the lumen. Second, the effects of specific transport inhibitors-ouabain, phloridzin, and acetazolamide-was ascertained when placed either on luminal or blood side. Isolated segments of rabbit PCT were perfused in vitro. Tubules perfused with isosmolar ultrafiltrate (UF) at rates > 10 nl/min had a mean PD of - 5.8+/-0.2 mV (lumen negative). Normal UF was simulated by an artificial perfusion solution. Using the latter, observed PD was - 5.4+/-0.2 mV. A significant reversible decrease in PD was noted when the following constituents were removed singly: glucose (from - 5.7+/-0.4 to - 3.5+/-0.4 mV); alanine (from - 5.8+/-0.4 to - 4.7+/-0.3 mV); and bicarbonate (from - 5.3+/-0.3 to - 3.3+/-0.5 mV). The combined removal of alanine and glucose (replaced with mannitol) reduced the transepithelial PD to - 0.5+/-0.1 mV with removal of glucose and alanine (replaced with mannitol) and decrease of NaHCO(3) to 5.6 meq/liter (replaced with NaCl), as normally occurs in early part of in vivo PCT, resulted in reversible change of PD from - 5.1+/-0.2 to + 3.2+/-0.2 mV. Ouabain (10(-5) M) reversibly decreased the negative control PD from blood side, but had no effect from luminal side. Phloridzin (10(-5) M) reversibly decreased PD from - 6.4+/-0.3 to - 3.7+/-0.4 mV when placed on luminal side but had minimal effect from blood side, - 6.3+/-0.4 to - 5.8+/-0.4 mV. Acetazolamide (Diamox) was without effect from either side. Reversal of bulk flow of water by addition of 31 mosmol/liter raffinose to perfusion ultrafiltrate did not significantly decrease the PD. It is concluded that specific pumps for transport of glucose, amino acids, and bicarbonate exist on the luminal surface. All three constituents are necessary for expression of maximum PD. Removal of these substrates by transport changes PD from - 5.1 mV to + 3.2 mV (lumen positive). This 3.2 mV positive PD is secondary to a chloride diffusion potential and is not effected by ouabain from the blood side.
Vascularization in the Healing of Fractures
Authors: Louis Lichtenstein
Journal: JAMA (1964)

This short monograph by a Dutch physician was printed in Holland and published simultaneously in this country. It is dedicated to obtaining good clinical results in the treatment of fractures through a better understanding of the importance of adequate vascularization in the development of callus and reconstruction. The experimental model was a fracture site in the distal portion of the rabbit tibia, and the meticulous studies in re-vascularization patterns were supplemented by observations on human fracture material. Three different methods of treatment were compared, namely, conservative treatment with application of a circular plaster cast, Küntscher's fixation employing an intramedullary nail, and Lane's plate and screws. With reference to fracture healing otherwise, the fundamental role of cartilage in the early phase of callus formation both in animals and in man was stressed. As for the clinical implications, it is emphasized that the chances of satisfactory healing are greatly dependent upon the
Slowing the speedy.
Authors: M. S. McGregor
Journal: BMJ (1988)

This short letter refutes the allegation that the way to reduce fatal traffic accidents is to vigorously enforce the current 70 mile per hour speed limit. It is suggested that one reason why as many as 40% of drivers ignore the speed limit is because it is safe to travel at higher speeds. A more pragmatic solution is suggested: a) raising the motorway speed limit to 84 miles per hour while vigorously enforcing urban speed limits near motorway exits and during bad weather; and b) improving the motorway network to prevent people speeding on dual carriageways.