tbuckley/cabot-search huggingface dataset:
Molecular Pathways: Myeloid Complicity in Cancer
Authors: Ingunn M. Stromnes, Philip D. Greenberg, Sunil R. Hingorani
Journal: Clinical Cancer Research (2014)

Cancer-induced inflammation results in accumulation of myeloid cells. These myeloid cells include progenitors and progeny of monocytes, granulocytes, macrophages, and dendritic cells. It has become increasingly evident that tumor-dependent factors can condition myeloid cells toward an immunosuppressive and protumorigenic phenotype. Thus, myeloid cells are not simply bystanders in malignancy or barometers of disease burden. Reflecting their dynamic and plastic nature, myeloid cells manifest a continuum of cellular differentiation and are intimately involved at all stages of neoplastic progression. They can promote tumorigenesis through both immune-dependent and -independent mechanisms and can dictate response to therapies. A greater understanding of the inherent plasticity and relationships among myeloid subsets is needed to inform therapeutic targeting. New clinical trials are being designed to modulate the activities of myeloid cells in cancer, which may be essential to maximize the efficacy of both conventional cytotoxic and immune-based therapies for solid tumors. Clin Cancer Res; 20(20); 5157-70. ©2014 AACR.
Effect of Digestible Carbohydrates on Glucose Control in Insulin-dependent Diabetic Patients
Authors: Nicola Perrotti, Donatella Santoro, Salvatore Genovese, Angela Giacco, Angela Rivellese, Gabriele Riccardi
Journal: Diabetes Care (1984)

Recent studies have demonstrated that high-carbohydrate—high-fiber diets may improve the metabolic control in diabetes. To evaluate the influence of dietary carbohydrates separate from dietary fiber on blood glucose control, six insulin-dependent diabetic patients (IDD) were assigned in random order to two weight-maintaining diets for consecutive periods of 10 days. The diets differed in carbohydrate (41% in diet A and 60% in diet B) and fat content (41% and 20%, respectively) but were identical in calories, proteins, simple sugars, and fiber. After each dietary period blood glucose was continuously monitored for 24 h (Biostator GCIIS, Life Science Instruments, Miles Laboratories, Elkhart, Indiana). The M value was 48 ± 20 after diet A and 96 ± 27 after diet B (t = 3.83, P &amp;lt; 0.025); the mean daily blood glucose was 152 ± 5 mg/dl after diet A and 206 ± 11 mg/dl after diet B (t = 7.50, P &amp;lt; 0.001). Similarly, the blood glucose level for the 3-h period after each of the three main meals was lower after diet A than after diet B (analysis of variance: F = 5.2, P &amp;lt; 0.05). No significant difference in fasting serum cholesterol, triglycerides, or serum lipoprotein composition was observed between the two diets. In order to separate the influence of dietary carbohydrate and fat on postprandial blood glucose concentration, an additional test meal experiment was performed in eight insulin-dependent diabetic patients. In random order on consecutive days they were given two standard meals that were identical in carbohydrate and protein content and differed only in the amount of olive oil added to the meals (12 g versus 36 g) The average blood glucose increments calculated for the 3h after the meal were almost identical after the high-fat and the low-fat test meal. It is concluded that increasing the amount of dietary carbohydrate leads to the deteriorationof blood glucose control in ID
Determinants of the Development of Diabetes (Maturity-Onset Diabetes of the Young-3) in Carriers of <i>HNF-1</i>α Mutations
Authors: Tomasz Klupa, James H. Warram, Anthony Antonellis, Marcus Pezzolesi, Moonsuk Nam, Maciej T. Malecki, Alessandro Doria, Stephen S. Rich, Andrzej S. Krolewski
Journal: Diabetes Care (2002)

OBJECTIVE—To determine the distribution of the age at onset of diabetes (maturity-onset diabetes of the young-3 [MODY3]) and to identify determinants of the onset of diabetes in carriers of HNF-1α mutations. RESEARCH DESIGN AND METHODS—Extended families (n = 104) with type 2 diabetes inherited in a dominant pattern were recruited and screened for diabetes-causing mutations in HNF-1α. RESULTS—HNF-1α mutations cosegregated with diabetes in only 13 families, all with a mean age at onset &amp;lt;35 years. Insulin secretion was diminished or absent in mutation carriers (n = 101), and diabetes developed in 65% by age 25 years and in 100% by age 50 years. If the mutation was inherited from the mother, diabetes onset was very young in those exposed to diabetes in utero; 57 ± 8% were affected by age 15 years as compared with 0.0% in those not exposed (P &amp;lt; 7 × 10−6). By age 25 years, the difference was reduced (85 ± 6 and 55 ± 12%, respectively; P = 0.02). If the mutation was inherited from the father, diabetes developed in 52 ± 8% by age 25 years. Age at diagnosis was shown to be highly heritable (h2 = 0.47, P = 0.003). When parent of origin was included in the analyses, the magnitude of genetic contribution increased markedly (h2 = 0.91). CONCLUSIONS—Mutations in HNF-1α accounts for diabetes in a small proportion of families with a dominant pattern of inheritance. Age at onset of diabetes in MODY3 families varied widely and was influenced by familial factors (including modifying genes) and parent of origin (whether a mutation carrier was exposed to diabetes in utero).
Passive expiration as a test of lung function.
Authors: K Ashutosh, J F Keighley
Journal: Thorax (1978)

Twenty-five normal subjects, 14 non-smokers and 11 smokers, passively expired into a spirometer after a maximal active inspiration, and after a passive inflation of the chest by a pressure cycled intermittent positive-pressure breathing (IPPB) machine. Acceptable passive expirations could be performed by all subjects after a passive inspiration but by only 12 after an active inspiration. Expired volume was found to change exponentially with time (r greater than 0.98), and the time constant of passive expiration (Tp) was obtained. There was no significant difference between the smokers and non-smokers in age, sex, forced vital capacity, FEV1 FEV1/FVC%, maximum mid-expiratory flow rate, maximum expiratory flow at 50% and 25% of the vital capacity, or the magnitude of the fall in the dynamic compliance with increasing frequency of breathing (Cdyn/f). Tp in smokers (1.06 +/- 0.47 SD) was significantly longer than in the non-smokers (0.65 +/- 0.25 SD P less than 0.02). Tp had a significant correlation with Cdyn/f(Tp = 0.6 + 161.81 Cdyn/f +/- 0.38 SE, r = 0.49, P less than 0.02). We conclude that satisfactory passive expiratory spirograms can be easily obtained after a mechanically assisted passive inspiration. Tp thus obtained is determined by the intrinsic properties of the respiratory system (lung plus thorax), and is significantly prolonged in smokers compared with non-smokers when other studies of pulmonary function including frequency dependence of compliance are unchanged.
Neovascularization induced by porous collagen scaffold implanted on intact and cryoinjured rat hearts
Authors: Andrea Callegari, Sveva Bollini, Laura Iop, Angela Chiavegato, Gianluca Torregrossa, Michela Pozzobon, Gino Gerosa, Paolo De Coppi, Nicola Elvassore, Saverio Sartore
Journal: Biomaterials (2007)
A novel inhalation allergen present in the working environment of beekeepers
Authors: O. Rudeschko, A. Machnik, H. Dörfelt, H.‐H. Kaatz, B. Schlott, R. W. Kinne
Journal: Allergy (2004)

Background: Inhalation allergies, caused by allergens from various kinds of pollen, house dust mites, animal epithelium, and mould fungi, are strongly increasing in frequency. In 2.6% of the cases the allergen source remains unidentified. The present paper describes a so far unknown inhalation allergy which was observed in the case of a patient working with hives. Methods and results: The allergen was characterized by immunoblotting, enzyme‐linked immunosorbent assay inhibition, and isoelectrofocusing, using the serum of the patient. It is present in both the bee bodies and the larvae, has a molecular mass of 13 kDa, and an isoelectric point of 5.85. It is thermolabile and does not cross‐react with allergens from birch, mugwort and timothy grass pollen, mould fungi, or bee venom. The N‐terminal amino acid sequence of allergen from larvae was determined to be 2 QIEELKTRLHT 12 . A similar allergen of 13 kDa was also found in Varroa mite accompanying bee populations. Conclusion: Honey bees (including the larva stadium) and Varroa mite contain a 13‐kDa protein causing an allergic reaction. Presently, there is no evidence whether the case described is a singular phenomenon or whether this allergen is a more common inducer of allergies among subjects exposed to honey bees. However, a bee and Varroa mite allergy has to be considered for beekeepers after exclusion of known inhalation allergies.
Hemolytic Effect of Therapeutic Drugs
Authors: Robert W. Kellermeyer
Journal: JAMA (1962)

FOR MANY YEARS hemolytic reactions have been recognized as hazards which accompany the administration of certain classes of therapeutic agents including sulfonamides, sulfones, benzene, and quinoline derivatives. Although some episodes of drug-induced hemolysis can be attributed to hypersensitivity, most reactions cannot be explained by an immune mechanism. In 1941 Emerson, Ham, and Castle suggested that some hemolytic drugs and chemical compounds, or their degradation products, functioned as oxidants in reversible oxidation-reduction systems in the erythrocytes and, thereby, caused methemoglobin formation, increased osmotic fragility, and hemolysis. Recently Jandl et al., showed, in vitro, that oxidant drugs capable of acting as redox intermediates oxidize hemoglobin, first reversibly to methemoglobin and eventually irreversibly to oxidation products resembling Heinz bodies; they postulated that administration of these drugs enhanced the oxidation of hemoglobin and other vital cellular components in vivo and, thus, interfered with cellular integrity. In 1926 Cordes reported the occurrence of hemolytic anemia in
A Study of Heart Sounds and Murmurs by Direct Heart Recordings
Authors: CHARLES A. BERTRAND, IAN G. MILNE, RICHARD HORNICK
Journal: Circulation (1956)

A method is described for recording heart sounds and murmurs on the surface of the heart chambers and great vessels. Studies were performed on normal dogs and in those with murmurs of known origin, chiefly pulmonic and aortic stenosis. In addition, the reappearance of the murmurs in such cases was studied, following the release of caval occlusion. It was found that the systolic murmur of pulmonic stenosis returned almost immediately after release of caval occlusion, whereas the aortic murmurs did not return until usually from six to 10 beats after release. This may provide a basis for the differentiation of right heart and left heart murmurs by a carefully controlled Valsalva maneuver.
Functional Separation of Pseudopod Extension and Particle Internalization during Fcγ Receptor–mediated Phagocytosis
Authors: Malcolm B. Lowry, Anne-Marie Duchemin, John M. Robinson, Clark L. Anderson
Journal: The Journal of Experimental Medicine (1998)

Receptors for the Fc portion of immunoglobulin (Ig)G (FcγR) mediate phagocytosis of IgG-opsonized particles by a process that can be divided into four major steps: receptor–ligand binding, pseudopod extension, internalization, and lysosomal fusion. We have expressed single classes of FcγR in COS fibroblasts to examine the structural determinants necessary to complete the four steps of phagocytosis. Using phase contrast, fluorescence, confocal, and electron microscopy we have demonstrated that FcγR-expressing COS cells can phagocytose in a manner similar to that of professional phagocytes. We have further analyzed the capacity of the three classes of FcγR to phagocytose, placing special emphasis on the FcγRIA–γ chain complex, which allowed us to examine independently the roles of the ligand-binding unit (FcγRIA) and the signaling unit (γ chain). We found that receptor complexes containing a conserved tyrosine activation motif (ITAM), as found in the cytoplasmic domain of FcγRIIA and in the γ chain associated with FcγRIA and FcγRIIIA, readily internalized target particles. In contrast, FcγRIA alone, having no ITAM, was unable to internalize target particles efficiently, but did mediate pseudopod extension. Cotransfection of γ chain with FcγRIA restored the ability of the receptor to internalize target particles. A mutant FcγRIA in which the cytoplasmic domain had been deleted was also capable of mediating pseudopod extension, showing that neither the γ chain nor the cytoplasmic domain of FcγRIA were required for this step. Cytochalasin D, an inhibitor of actin polymerization, blocked particle internalization by all FcγR, but did not block pseudopod extension. Staining the FcγRIA COS cells for F-actin and for tyrosine phosphoproteins, we found that actin did not polymerize during FcγRIA-mediated pseudopod extension, nor were tyrosine kinases activated. Our data suggest that pseudopod extension and internalization are functionally distinct steps mediated through different pathways.
Confirmation of asthma diagnosis in the community
Authors: A. D'Urzo
Journal: European Respiratory Journal (2010)

powers.No doubt, new studies will utilise the revised version of the Geneva model.As for the Wells score used in our study, we think that neither dichotomised nor trichotomised scores make too much sense if they are combined with a D-dimer test.It must be noted that positive D-dimer test allows the shifting of some patients from the ''unlikely'' PE arm of the dichotomised Wells score back to the ''likely'' arm.Since only few COPD studies related to the Wells scoring system exist in the literature, we preferred including all COPD patients for evaluation who are considered naturally at risk for PE, as mentioned above, to excluding some unlikely PE patients with negative D-dimer test results.We believe this approach would be necessary for the further validation of the Wells system in this specific group of patients.As a complicating or triggering factor, presence of VTE in COPD patients on exacerbation is an important issue.1-yr mortality was found doubled in VTE cases in our study.We believe that clinical prediction rules developed for PE will help us to manage COPD.As L. Bertoletti and M. Righini also underline, in order to have better prediction powers in cases with severe underlying specific diseases, we might need some modifications in the current prediction models, or some new disease-specific models should be developed in future.
Costly referral management centres fail to deliver savings
Authors: O. Mashta
Journal: BMJ (2010)

NHS referral management centres, set up to manage referrals from GPs to secondary care, which cost millions of pounds, are failing to deliver savings, the health policy think tank the King’s Fund has said.

In some instances the centres are undermining quality by misdirecting referrals in the absence of full clinical information or by delaying access to a specialist, the research by the King’s Fund found.

Candace Imison, deputy director of policy at the King’s Fund, said, “We found that the most interventionist management approaches from PCTs [primary care trusts], such as referral management centres, were unlikely …
The immunoregulatory role of CD244 in chronic hepatitis B infection and its inhibitory potential on virus-specific CD8+ T-cell function
Authors: Bijan Raziorrouh, Winfried Schraut, Tilman Gerlach, Daniela Nowack, Norbert H. Grüner, Axel Ulsenheimer, Reinhart Zachoval, Martin Wächtler, Michael Spannagl, Jürgen Haas, Helmut M. Diepolder, Maria-Christina Jung
Journal: Hepatology (2010)

Multiple inhibitory receptors may play a role in the weak or absent CD8+ T-cell response in chronic hepatitis B virus (HBV) infection. Yet few receptors have been characterized in detail and little is known about their complex regulation. In the present study, we investigated the role of the signaling lymphocyte activation molecule (SLAM)-related receptor CD244 and of programmed death 1 (PD-1) in HBV infection in 15 acutely and 66 chronically infected patients as well as 9 resolvers and 21 healthy controls. The expression of CD244, PD-1, and T-cell immunoglobulin domain and mucin domain 3 (TIM-3) was analyzed in virus-specific CD8+ T-cells derived from peripheral blood or liver using major histocompatibility complex class I pentamers targeting immunodominant epitopes of HBV, Epstein-Barr-virus (EBV), or influenza virus (Flu). In chronic HBV infection, virus-specific CD8+ T-cells expressed higher levels of CD244 both in the peripheral blood and liver in comparison to the acute phase of infection or following resolution. CD244 was expressed at similarly high levels in EBV infection, but was low on Flu-specific CD8+ T-cells. In chronic HBV infection, high-level CD244 expression coincided with an increased expression of PD-1. The inhibition of the CD244 signaling pathway by antibodies directed against either CD244 or its ligand CD48 resulted in an increased virus-specific proliferation and cytotoxicity as measured by the expression of CD107a, interferon-γ, and tumor necrosis factor-α in CD8+ T-cells. Conclusion: CD244 and PD-1 are highly coexpressed on virus-specific CD8+ T-cells in chronic HBV infection and blocking CD244 or its ligand CD48 may restore T-cell function independent of the PD-1 pathway. CD244 may thus be another potential target for immunotherapy in chronic viral infections. (HEPATOLOGY 2010)
Immunocytochemical staining of breast carcinoma with the monoclonal antibody NCRC 11: a new prognostic indicator.
Authors: I O Ellis, C P Hinton, J MacNay, C W Elston, A Robins, A A Owainati, R W Blamey, R W Baldwin, B Ferry
Journal: BMJ (1985)

The staining of breast cancer with a new monoclonal antibody, NCRC 11, was studied in a series of 126 women with primary breast carcinoma. Tumour samples embedded in paraffin were tested, and the minimum duration of follow up was five years or to death. Altogether 119 tumours stained positively. There was a strong relation between the intensity of staining, divided on a four point scale, and patient survival. Patients whose tumours exhibited intense staining had an improved survival compared with those with less intensely staining tumours (p less than 0.0001). Staining related weakly to histological grade but not significantly to oestrogen receptor state or the pathological stage of lymph node disease. Mathematical analysis showed the relation to survival to be independent of the other known prognostic factors. Inclusion of intensity of staining with other factors in a prognostic index might permit a more accurate estimation of prognosis in patients with breast cancer.
Complement Research
Authors: Herbert J. Rapp
Journal: JAMA (1966)

About 80 years ago it was discovered that fresh b blood serum is bactericidal.<sup>1</sup>Subsequently, it was found that fresh blood serum is capable of lysing erythrocytes,<sup>2</sup>protozoa,<sup>3</sup>and tumor cells.<sup>4</sup>This lytic activity is the result of the interaction of antigens located on the surface of the cell, corresponding serum antibodies, serum complement, and calcium and magnesium ions.<sup>5</sup>The result of these interactions is the formation of discrete lesions on the surface of the cell.<sup>6</sup>There is evidence suggesting that low molecular weight substances pass through these lesions causing an osmotic imbalance leading to rupture of the cell.<sup>7</sup> Much of the newer knowledge about complement has come from application of modern tools of molecular biology to the study of immune cytolysis. As this newer knowledge has emerged, there has been renewed interest in studies on the participation of complement in a variety
The Ethics of Addiction
Authors: THOMAS S. SZASZ
Journal: American Journal of Psychiatry (1971)

The author believes and attempts to demonstrate that "drug abuse" and "drug addiction" are moral rather than medical problems. The basic issue underlying these problems is: In a conflict between the individual and the state, where should the individual's autonomy end and the state's right to intervene begin? The author suggests that genuine commitment to the ethic of personal freedom and responsibility requires that, much as we may disapprove of a person's choice of drug, we must regard freedom of self-medication as a fundamental right.
78 Resolution of the β-adrenoceptor (BAR) regulating activity in A549 lung cells of lymphocyte conditioned medium (LCM) derived from cultured IM9 cells with deae ion exchange HPLC
Authors: A SZENTIVANYI, M SCHULTZE, O HEIM, S REINER, S ROBICSEK, J ZORITY, J HACKNEY, R LOCKEY
Journal: Journal of Allergy and Clinical Immunology (1991)
UK government promises bill to reform English libel law
Authors: C. Dyer
Journal: BMJ (2010)

The government hopes to introduce legislation next year to reform English libel law to protect freedom of speech and scientific debate, the justice minister, Tom McNally, has announced in the House of Lords.

Speaking at the end of the second reading debate on the private member’s Defamation Bill promoted by the Liberal Democrat peer Anthony Lester ( BMJ 2010;340:c3284, doi:10.1136/bmj.c3284), Lord McNally said that the government would consult on the issue over the summer.

However, it would not simply adopt Lord Lester’s bill but would bring forward its own draft bill for consultation and pre-legislative scrutiny in the new year, with a view …
Would recording family history of postpartum haemorrhage make any difference?
Authors: S. L. Sholapurkar
Journal: BMJ (2014)

Oberg and colleagues’ study on the genetic contribution to the common condition of postpartum haemorrhage (PPH) analysed 466 686 births using elaborate statistical modelling.1 Did this study have a “control” group, or was one not needed? Did this study analyse births without PPH and show a lack of “familial clustering of PPH” in these?

The size of the increased risk of PPH with different …
Single Versus Divided Daily Dose of Trimipramine in the Treatment of Depressive Illness
Authors: M. Z. HUSSAIN, Z. A. CHAUDHRY
Journal: American Journal of Psychiatry (1973)

A group of 56 patients with depressive illnesses were administered either a single daily dose or a divided daily dose of trimipramine on a random basis. Results of the treatment showed several advantages for the use of a single daily dose: a trend toward better therapeutic improvement, a significant decrease in the side effects of insomnia and fatigue, and more regular consumption of the medication.
U.S. army medical department in the second world war
Authors: A. P. Thomson
Journal: BMJ (1969)

the summarisation and organisation of material."The details which the author considers least essential have been presented in smaller print.Some figures have been eliminated while others have been enlarged.The presentation of the subject is essentially on a regional basis, the book having been divided into the following nine sections: general concepts in anatomy, upper limb, head and neck, back, chest, abdomen, perineum, pelvis, and lower limb.Nevertheless, the author has endeavoured, where possible, to relate the regional descriptions with a systemic approach.