tbuckley/cabot-search huggingface dataset:
Epitope mapping of the cat (<i>Felis domesticus</i>) major allergen <i>Fel d</i> I by overlapping synthetic peptides and monoclonal antibodies against native and denatured <i>Fel d</i> I
Authors: W. van't Hof, F. J. van Milligen, M. van den Berg, M. Lombardero, M. D. Chapman, R. C. Aalberse
Journal: Allergy (1993)

The major cat allergen Fel d I is a homodimer of which each monomer consists of two disulfide‐linked polypeptide chains: chain 1 (70 amino acid residues) and chain 2 (92 amino acid residues). Twenty‐one synthetic peptides of 14 amino acid residues length, overlapping by seven residues and spanning the entire sequence of both chains, were synthesized. These peptides were coupled to CNBr‐activated Sepharose‐4B and used as solid‐phase antigens in epitope‐mapping studies with monoclonal antibodies against native and reduced/alkylated Fel d I. Two monoclonal antibodies directed against reduced/alkylated chain I bound to the overlapping peptides 53–66 and 60–70 of chain 1. The monoclonal antibody directed against reduced/alkylated chain 2 bound to the overlapping peptides 36–49 and 43–56 of chain 2. Binding specificity was demonstrated by inhibition by reduced/alkylated Fel d I for all three monoclonal antibodies. Another monoclonal antibody against reduced/alkylated Fel d I had been found to bind predominantly to reduced/alkylated chain 2 on immunoblot in previous studies (27). It bound to peptides 1–16 and 60–70 of chain 1 and peptides 1–14 and 50–63 of chain 2; it is therefore probably directed against a conformational epitope formed by these four regions. Possibly because of low affinity of this monoclonal antibody, specificity of its binding could not be verified by inhibition studies. A panel of monoclonal antibodies directed against native Fel d I bound to peptides 1‐16 and 60–70 of chain 1 and peptides 1–14 and 43–56 of chain 2. For two monoclonal antibodies, binding to each peptide was investigated and shown to be inhibitable by native Fel d I. These antibodies are therefore probably directed against a conformational epitope formed by these four regions. These studies give us substantial information about the quaternary structure of Fel d I.
THE IMPACT OF POSTPROCEDURAL INTRAVASCULAR ULTRASOUND FINDINGS ON LONG-TERM RESULTS FOLLOWING SELF-EXPANDABLE NITINOL STENTING IN THE SUPERFICIAL FEMORAL ARTERY
Authors: Kojiro Miki, Kenichi Fujii, Daizo Kawasaki, Masashi Fukunaga, Tsuyoshi Nakata, Masahiko Shibuya, Mitsumasa Ohyanagi, Tohru Masuyama
Journal: Journal of the American College of Cardiology (2012)
Effects of beta-adrenergic blockade on the cardiac response to maximal and submaximal exercise in man.
Authors: S Epstein, B F Robinson, R L Kahler, E Braunwald
Journal: Journal of Clinical Investigation (1965)

Many of the changes in cardiac performance that take place during exercise resemble those that result from stimulation of the sympathetic nervous pathways to the heart.It has therefore been thought likely that an increase in sympathetic nervous activity occurs during exercise and is important in the mediation of the associated cardiac response.To test this hypothesis a variety of experimental approaches have been employed.Sev- eral investigators have studied the manner in which surgical denervation of the heart in the dog affects its performance during exercise (1-7), and others have examined the effects of a variety of antiadrenergic drugs on the response to exercise in man (8-12).The results have been conflicting, with some groups ascribing little, if any, impor- tance to the sympathetic system in the over-all performance of the heart (1, 2, 4, 6, 7, 9-11), whereas others believe that the sympathetic nerves do play a major role (3, 5, 8).The interpretation of these earlier studies is complicated.In several of the experiments utiliz- ing surgical denervation, section of the sympathetic nerves was not confined to those innervating the heart (1-3, 5).In others, the parasympathetic innervation of the heart was also interrupted (4-7), and some experiments were performed un- der general anesthesia (3).Furthermore, it is quite unknown to what extent conclusions based on studies in the dog can be applied to exercising man.In previous investigations on human sub- jects in which guanethidine or syrosingopine was administered, the sympathetic blockade involved not only the heart but the venous and arterial beds as well (8, 12).The recent development of spe-
Psychological and social effects of myocardial infarction on wives.
Authors: H G Kinnell
Journal: BMJ (1978)

provided that there is no special morbidity associated with its use.The experience of Sculco and Ranawat4 with spinal anaesthesia has been encouraging and this technique is now being used in Gartnavel.Our results so far indicate that when spinal anaesthesia is used the operative blood loss and the post- operative DVT rate are both reduced by about 50% compared with general anaesthesia.
Preliminary Clinical Assessment of I.C.R.F. 159 in Acute Leukaemia and Lymphosarcoma
Authors: K. Hellmann, K. A. Newton, D. N. Whitmore, I. W. F. Hanham, J. V. Bond
Journal: BMJ (1969)

I.C.R.F. 159, a new antitumour agent, has been assessed in six patients with acute leukaemia and three with lymphosarcoma. In all but two there was a considerable fall in circulating primitive cells, and in one there was bone-marrow evidence of a partial remission. Severe toxic effects were seen in only one case; they consisted of alopecia and gastroenteritis. It is suggested that I.C.R.F. 159 is worth further examination in all forms of acute leukaemia and lymphosarcoma.
EDUCATION AS A FACTOR IN THE PREVENTION OF CRIMINAL ABORTION AND ILLEGITIMACY.
Authors: HENRY O. MARCY
Journal: JAMA (1906)

A distinguished physician once said to me that he did not understand why there was implanted so strongly in both sexes the passionate desire for sexual relationship, while at the same time its gratification was hedged about by so many dangers and penalties. I suppose this thought has been prominent in the minds of all wise men during the history of the race, from savagery to the present. Many-sided views have been expressed by previous speakers. Few questions pertaining to the civilization of the present are more important or have a greater influence for good or bad on the higher development of man. <h3>EDUCATION THE NEED.</h3> The only thing which I wish to emphasize at present is that every young man and young woman should be intelligently taught during the period of education, commencing at puberty, the meaning and possibilities of the sexual relationship. The inherent forces of Nature compel
Little progress has been made in combating hospital infections
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

The NHS has failed to confront the problem of hospital acquired infections, focusing too much on methicillin resistant Staphylococcus aureus (MRSA) and failing to adequately implement strategies to fight the spread of infections among patients, says a cross party group of MPs.

The House of Commons Public Accounts Committee this week delivered its highly critical report on reducing the risk of hospital acquired infections. The report examines the progress made by the Department of Health and NHS …
Statin enhances cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cells
Authors: Y. Hattori, N. Nakanishi, K. Kasai
Journal: Cardiovascular Research (2002)

We investigated the effects of the statins, cerivastatin and fluvastatin, on the induction of nitric oxide (NO) production in vascular smooth muscle cells (VSMC) stimulated by interleukin-1beta (IL-1) or in combination with interferon-gamma (IFN).We measured NO release, inducible NO synthase (iNOS) mRNA and protein levels, iNOS gene transcription rates, and iNOS mRNA stabilities in cytokine-activated VSMC. We also evaluated nuclear factor (NF)-kappaB activity and tetrahydrobiopterin (BH4) synthesis.NO production induced by cytokines was dose-dependently enhanced by both statins. Incubating VSMC with IL-1/IFN stimulated iNOS mRNA and protein expression. Both statins significantly upregulated IL-1/IFN-stimulated iNOS mRNA and protein expression, and enhanced iNOS gene transcription as shown by nuclear run-on assays. However, they did not alter the stability of iNOS mRNA. Both statins slightly modulated IL-1/IFN-induced NF-kappaB activation, which was not associated with their effect on NO production. Cytokines induce the de novo synthesis of BH4 in VSMC. This event is essential for the induction of NO synthesis, which requires transcriptional induction of the genes that encode not only iNOS but also guanosine triphosphate cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in de novo BH4 synthesis. The synthesis of BH4 and GTPCH mRNA induced by IL-1/IFN were enhanced by both statins. Exogenous mevalonate significantly prevented and geranylgeranylpyrophosphate reversed the stimulatory effect of both statins. Furthermore, the geranylgeranyltransferase I inhibitor GGTI-298 significantly increased IL-1/IFN-induced NO production.Our data demonstrated that statins enhance immunostimulants-induced NO production by increasing iNOS gene expression at the transcriptional level via an NF-kappaB-independent pathway. The effect of statins on NO production is due at least partly through blocking the biosynthesis of mevalonate, which prevents isoprenoid biosynthesis. In addition to augmenting iNOS expression, statins potentiate GTPCH gene expression and BH4 synthesis, thereby preventing a relative shortage of BH4 which may shift the balance between NOS-catalyzed generation of protective NO and deleterious reactive oxygen species.
Cardiac Failure with Reserpine
Authors: E. Marley, C. M. B. Pare
Journal: BMJ (1956)

Reserpine (" serpasil ") is a colourless crystalline ester- alkaloid derived from the roots of Rauwolfia serpentina, and is useful both as a hypotensive agent and as a seda- tive in psychiatric practice.During the treatment of out-patients attending hospital we were surprised to dis- cover two cases of cardiac failure occurring apparently in association with the administration of this drug.The two relevant case histories are presented.The results of the investigations suggest that reserpine causes a re- tention of fluid in the body, a factor which may result in heart failure in susceptible subjects.Case 1 A housewife aged 38 developed severe hypertension fol- lowing toxaemia of pregqancy, and on account of rapid deterioration in her condition had been subjected to bilateral sympathectomy during 1953.She had, in addition, a past history of depressive episodes necessitating treatment with electroplexy, having been only recently discharged from hospital for this reason.At a follow-up 0.25 mg. of reser- pine three times a day was prescribed, and over the next seven weeks she again became depressed, with the appear- ance of minimal ankle oedema.On examination the jugular venous pressure was not raised, the blood pressure being 170/110.The apical im- pulse was heaving in character and lay in the sixth left intercostal space outside the mid-clavicular line.The liver was not palpable, there was no ascites, and the lung bases were clear.Two weeks later she became much more depressed and complained of breathlessness on exertion.The jugular venous pressure was 3 cm.above the sterno-clavicular angle
In vitro culture with prednisolone increases BCL-2 protein expression in adult acute lymphoblastic leukemia cells
Authors: Patrizia Tosi, Giuseppe Visani, Emanuela Ottaviani, Silvia Manfroi, Sante Tura
Journal: American Journal of Hematology (1996)

The presence of BCL-2 gene rearrangement has been detected also in cellular populations lacking the t(14;18) chromosomal translocation, such as B-lineage acute lymphoblastic leukemia (ALL) cells. It has been reported that overexpression of BCL-2 is related to resistance to glucocorticoid-induced apoptosis. In this study, we aimed to evaluate whether in vitro culture with prednisolone (PDN) could modify the expression of BCL-2 protein. ALL cells from 21 patients were incubated for 72 hr with or without a minimally lethal (IC12) dose of PDN. In vitro culture with PDN did not affect the percentage of positive cells, even though the mean fluorescence index was significantly increased (P = 0.0001), thus indicating a higher level of protein production. These data could suggest a possible mechanism of drug resistance after treatment with PDN. © 1996 Wiley-Liss, Inc.
Cost of Teaching Medical Students-Reply
Authors: Ethel Weinberg
Journal: JAMA (1995)

In Reply.  —Dr Sperry is correct in noting that we used average costs rather than marginal costs in our discussion of replacement costs for teaching at nonuniversity hospitals.  Marginal costs seemed inappropriate for at least two reasons. First, many university hospitals could not accommodate all of the medical students, particularly in obstetrics and pediatrics. Other locations with attendant new administrative costs would be sought. Second, much of the teaching of third-year medical students is in very small groups. For example, the highest mean daily hours was for supervising students in the outpatient setting. In this situation the teacher-to-student ratio was only 1 to 21. It would be false to assume that the university faculty would simply absorb the new students without adding faculty costs. The latter represent almost two thirds of the costs in our study. It is certainly true that there is inequality of cost structures in different centers,
Reproductive Mortality and Oral Contraceptives-Reply
Authors: Peter M. Layde
Journal: JAMA (1983)

In Reply.—  Drs Rosenfield and Cushner make a number of useful comments that help the reader correctly interpret our analysis of reproductive mortality in the United States. They also say our article implied that the number of reproductive deaths may be reduced by half if women stop using oral contraceptives—we did not intend to imply this. As they correctly point out, a small group of oral contraceptive users, women 35 years of age and older who smoke, have a high risk of pill-related mortality and account for most deaths caused by oral contraceptives. For women in this group, the risk of oral contraceptive use appears to far outweigh the risk of pregnancyassociated mortality. If this small group stops using oral contraceptives, most of the pill-related deaths can be eliminated.  Our analysis of reproductive mortality does not consider the recently identified noncontraceptive benefits of oral contraceptives. The reproductive mortality rate is
Are State Mortality Differences due to Migration From the Rust Belt?
Authors: Frank J. Richter
Journal: JAMA (1991)

To the Editor.—  Hahn et al 1 rank the 50 states by their combined mortality rates from nine chronic diseases. Excess deaths for each state were calculated on the basis of this ranking. The flaw of this study is that it presents age-adjusted death rates in 1986 based on 1980 population. This approach ignores changes in the age structure of states from 1980 through 1986.  The early 1980s were a period of great interstate migration, due in part to the 1982 recession. Young people (eg, aged 25 through 29 years) were nearly five times more likely to move to another state than people aged 65 years and older. 2 Thus, states with high levels of out-of-state migration in the early 1980s had older populations with higher mortality risks per capita by 1986. The result is a skewed statistical ranking that makes the death rates in Rust Belt states seem higher
Hydroxyurea‐induced splenic regrowth in an adult patient with severe hemoglobin SC disease
Authors: Yiwu Huang, Thyagarajan Ananthakrishnan, Joseph E. Eid
Journal: American Journal of Hematology (2003)

Abstract Hydroxyurea has been extensively used in patients with sickle cell anemia and severe sickle cell‐hemoglobin C (SC) disease to reduce the severity of their diseases. We report here our experience with an adult patient with severe SC disease who developed symptomatic splenomegaly requiring splenectomy while being treated with hydroxyurea. This case suggests that hydroxyurea might restore some splenic function in functionally asplenic patients with sickle cell anemia or SC disease, but also raises the clinical concern that hydroxyurea may induce splenic regrowth, resulting in symptomatic splenomegaly. With the increasing use of hydroxyurea in the management of SS disease or other hemoglobinopathies, the importance of spleen monitoring must be further emphasized in these patients. Am. J. Hematol. 74:125–126, 2003. © 2003 Wiley‐Liss Inc.
The immune response of phiX 174 in man. III. Evidence for an association between hyposplenism and immunodeficiency in patients with coeliac disease.
Authors: P G Baker, J V Jones, D B Peacock, A E Read
Journal: Gut (1975)

The ability of patients with coeliac disease to produce primary and secondary antibody in response to a new antigen has been tested. Eight patients with coeliac disease were injected intravenously with the coliphage phiX 174. Antibody levels were measured throughout the primary response. On day 28 a second injection was given and the secondary response was also studied in detail. The production of antibody in the primary response is lower than in a group of normal subjects. The secondary response is severely reduced and the difference between the coeliac group and controls is highly significant. The secondary response in the coeliac patients contains a much higher proportion of IgM antibody than normal. These abnormalities correlate approximately with clinical status and with hyposplenism. It is concluded that in patients with coeliac disease the ability to produce antibody is impaired, with a defect in switching from IgM to IgG antibody.
A NEW INSTRUMENT FOR TRANSFUSION OF WHOLE BLOOD
Authors: A. L. Soresi
Journal: JAMA (1925)

The apparatus here described has these essential features: There is automatic infallible control of the passage of whole blood from donor to recipient. This is exercised by two valves acting solely under the force of gravity. Only one small 2 c.c. syringe, which is never changed during the whole procedure, is required. All the more or less complicated maneuvers common to other apparatus and methods, such as continuous washing and changing of syringes, sprinkling the syringe with ether, switching plates, opening or closing stopcocks, and clamping rubber tubings are eliminated. The surgeon can do the most satisfactory transfusion all alone. All he has to do is to insert one needle in the vein of the donor and the other in the vein of the recipient, and push back and forth the plunger of the syringe. The passage of the blood from donor to recipient is automatically controlled. The whole apparatus
S124 Derivation and validation of the bronchiectasis severity index: an international multicentre observational study
Authors: JD Chalmers, P Goeminne, S Aliberti, M McDonnell, S Lonzi, J Davidson, L Poppelwell, W Salih, A Pesci, L Dupont, TC Fardon, A De Soyza, AT Hill
Journal: Thorax (2013)

<h3>Introduction</h3> There are no risk stratification tools for morbidity and mortality in bronchiectasis. As more treatments become available, it is important to identify patients at risk of exacerbations, hospital admissions and mortality to target novel therapies. <h3>Methods</h3> A prospective observational study at a specialist bronchiectasis clinic in Edinburgh, UK was used to derive a bronchiectasis severity index using cox-proportional hazards regression to identify independent predictors of mortality and hospital admission over 4 years follow-up. Averaged ß-coefficients were used to award points for each independent variable and the discrimination of a derived score was tested using the area under the receiver operator characteristic curve (AUC). The score was validated in independent cohorts from Dundee, UK (N = 218), Leuven, Belgium (N = 253), Monza, Italy (N = 105) and Newcastle, UK (N = 126). <h3>Results</h3> 608 patients were included in the derivation cohort. Independent predictors of future hospital admissions were prior hospital admissions hazard ratio (HR) 13.5 (9.40–19.46), MRC dyspnoea score &gt; 4, HR 2.42 (1.66–3.52), FEV<sub>1 </sub>&lt;30% predicted HR 1.52 (1.03–2.25), <i>Pseudomonas aeruginosa </i>colonisation HR 2.16 (1.36–3.43), colonisation with other organisms HR 1.66 (1.12–2.44) and &gt; 3 lobes involved on HRCT HR 1.48 (1.02–2.15). In the model for mortality, independent predictors were Age &gt;70 years 8.57 (1.15–63.63), FEV<sub>1</sub> &lt;30% predicted HR 4.47 (1.60–12.53), prior hospital admissions HR 2.43 (1.30–4.53) and 3 or more exacerbations per year prior to the study HR 2.03 (1.02–4.03). The bronchiectasis severity index derived from these models was composed of prior hospitalisation (5 points), MRC dyspnoea score (0–3 points), FEV<sub>1</sub> (0–3 points), bacterial colonisation (0- 3 points) Age (0–6 points) BMI &lt;18.5 (2 points) Exacerbation frequency (0–2 points) and radiological extent (1 point). The AUC for mortality was 0.80 (0.74–0.86) and the AUC for hospitalisation was 0.88 (0.84–0.91). There was a clear difference in exacerbation frequency and quality of life using the St. Georges Respiratory Questionnaire between patients classified as low, intermediate and high risk by the score (p &lt; 0.0001 for all comparisons). In the validation cohorts, the AUC for mortality ranged from 0.81–0.84 and for hospitalisation was AUC 0.80–0.88. <h3>Conclusions</h3> The bronchiectasis severity index identifies patients at risk of future mortality, hospital admissions and exacerbations.
Kruppel-like factor 15 is critical for vascular inflammation
Authors: Yuan Lu, Lisheng Zhang, Xudong Liao, Panjamaporn Sangwung, Domenick A. Prosdocimo, Guangjin Zhou, Alexander R. Votruba, Leigh Brian, Yuh Jung Han, Huiyun Gao, Yunmei Wang, Koichi Shimizu, Kaitlyn Weinert-Stein, Maria Khrestian, Daniel I. Simon, Neil J. Freedman, Mukesh K. Jain
Journal: Journal of Clinical Investigation (2013)

Activation of cells intrinsic to the vessel wall is central to the initiation and progression of vascular inflammation. As the dominant cellular constituent of the vessel wall, vascular smooth muscle cells (VSMCs) and their functions are critical determinants of vascular disease. While factors that regulate VSMC proliferation and migration have been identified, the endogenous regulators of VSMC proinflammatory activation remain incompletely defined. The Kruppel-like family of transcription factors (KLFs) are important regulators of inflammation. In this study, we identified Kruppel-like factor 15 (KLF15) as an essential regulator of VSMC proinflammatory activation. KLF15 levels were markedly reduced in human atherosclerotic tissues. Mice with systemic and smooth muscle-specific deficiency of KLF15 exhibited an aggressive inflammatory vasculopathy in two distinct models of vascular disease: orthotopic carotid artery transplantation and diet-induced atherosclerosis. We demonstrated that KLF15 alters the acetylation status and activity of the proinflammatory factor NF-κB through direct interaction with the histone acetyltransferase p300. These studies identify a previously unrecognized KLF15-dependent pathway that regulates VSMC proinflammatory activation.