tbuckley/cabot-search huggingface dataset:
An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen
Authors: J. Temelkovski, S. P Hogan, D. P Shepherd, P. S Foster, R. K Kumar
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Existing murine models of asthma lack many of the inflammatory and epithelial changes that are typical of the human disease. Moreover, these models are frequently complicated by allergic alveolitis. <h3>METHODS</h3> High IgE responder BALB/c mice were systemically sensitised to ovalbumin and chronically challenged with low particle mass concentrations of aerosolised ovalbumin. Titres of anti-ovalbumin IgE in serum were measured at two weekly intervals by enzyme immunoassay, accumulation of inflammatory cells and histopathological abnormalities of the epithelium were quantified morphometrically in the trachea and the lungs, and airway reactivity was assessed by measuring bronchoconstriction following intravenous administration of methacholine. <h3>RESULTS</h3> Mice sensitised by two intraperitoneal injections of ovalbumin developed high titres of IgE antibodies to ovalbumin. Following exposure to low concentrations of aerosolised antigen for up to eight weeks these animals developed a progressive inflammatory response in the airways, characterised by the presence of intraepithelial eosinophils and by infiltration of the lamina propria with lymphoid/mononuclear cells, without associated alveolitis. Goblet cell hyperplasia/metaplasia was induced in the intrapulmonary airways, while epithelial thickening and subepithelial fibrosis were evident following chronic exposure. In parallel, the mice developed increased sensitivity to induction of bronchospasm, as well as increased maximal reactivity. Non-immunised mice exposed to aerosolised ovalbumin had low or absent anti-ovalbumin IgE and did not exhibit inflammatory or epithelial changes, but developed airway hyperreactivity. <h3>CONCLUSIONS</h3> This experimental model replicates many of the features of human asthma and should facilitate studies of pathogenetic mechanisms and of potential therapeutic agents.
Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes
Authors: Umberto Veronesi, Giovanni Paganelli, Viviana Galimberti, Giuseppe Viale, Stefano Zurrida, Marilia Bedoni, Alberto Costa, Concetta de Cicco, James G Geraghty, Alberto Luini, Virgilio Sacchini, Paolo Veronesi
Journal: The Lancet (1997)
Association of Numeracy and Diabetes Control
Authors: Kerri Cavanaugh, Mary Margaret Huizinga, Kenneth A. Wallston, Tebeb Gebretsadik, Ayumi Shintani, Dianne Davis, Rebecca Pratt Gregory, Lynn Fuchs, Robb Malone, Andrea Cherrington, Michael Pignone, Darren A. DeWalt, Tom A. Elasy, Russell L. Rothman
Journal: Annals of Internal Medicine (2008)

The influence of a patient's quantitative skills (numeracy) on the management of diabetes is only partially understood.To examine the association between diabetes-related numeracy and glycemic control and other diabetes measurements.Cross-sectional survey.2 primary care and 2 diabetes clinics at 3 medical centers.398 adult patients with type 1 or type 2 diabetes mellitus enrolled between March 2004 and November 2005.Health literacy, general numeracy, and diabetes-related numeracy assessed by using the Rapid Estimate of Adult Literacy in Medicine; the Wide Range Achievement Test, 3rd edition; and the Diabetes Numeracy Test (DNT), respectively. The primary outcome was most recent level of hemoglobin A1c. Additional measurements were diabetes knowledge, perceived self-efficacy of diabetes self-management, and self-management behaviors.The median DNT score was 65% (interquartile range, 42% to 81%). Common errors included misinterpreting glucose meter readings and miscalculating carbohydrate intake and medication dosages. Lower DNT scores were associated with older age, nonwhite race, fewer years of education, lower reported income, lower literacy and general numeracy skills, lower perceived self-efficacy, and selected self-management behaviors. Patients scoring in the lowest DNT quartile (score <42%) had a median hemoglobin A1c level of 7.6% (interquartile range, 6.5% to 9.0%) compared with 7.1% (interquartile range, 6.3% to 8.1%) in those scoring in the highest quartile (P = 0.119 for trend). A regression analysis adjusted for age, sex, race, income, and other factors found a modest association between DNT score and hemoglobin A1c level.Causality cannot be determined in this cross-sectional study, especially with its risk for unmeasured confounding variables.Poor numeracy skills were common in patients with diabetes. Low diabetes-related numeracy skills were associated with worse perceived self-efficacy, fewer self-management behaviors, and possibly poorer glycemic control.
Thromboxane receptor blockade attenuates chronic cyclosporine nephrotoxicity and improves survival in rats with renal isograft.
Authors: N Perico, M Rossini, O Imberti, B Malanchini, R P Cornejo, F Gaspari, T Bertani, G Remuzzi
Journal: Journal of the American Society of Nephrology (1992)

The question of whether pharmacological inhibition of the thromboxane A2 activity prevents cyclosporine-induced chronic renal dysfunction in a Lewis rat model of renal isograft was addressed. Transplanted animals were given a daily oral dose of cyclosporine (20 mg/kg; N = 15), cyclosporine (20 mg/kg) and the thromboxane A2 receptor antagonist GR32191 (3 mg/kg twice daily, by gavage; N = 15), or the vehicle alone (N = 12). Treatments were started the day of kidney transplant, and animals were monitored for 1 year. Cyclosporine-treated animals developed renal insufficiency, as documented by serum creatinine levels of 0.49 +/- 0.09, 0.95 +/- 0.12, and 1.38 +/- 0.15 mg/dL before and after 6 and 12 months of observation, respectively. Cyclosporine and GR32191 used in combination partially but significantly prevented the deterioration of renal function (serum creatinine, basal, 0.52 +/- 0.06; month 6, 0.68 +/- 0.04; month 12, 0.93 +/- 0.10 mg/dL). At the end of the study, GFR, as insulin clearance, was significantly lower in rats given cyclosporine (0.28 +/- 0.09 mL/min/100 g) than in rats given cyclosporine plus GR32191 (0.45 +/- 0.05 mL/min/100 g) or than in vehicle-treated animals (0.56 +/- 0.07 mL/min/100 g). Similar results were obtained for the effective RPF, measured as p-aminohippurate clearance. At the same time points, comparable to whole-blood cyclosporine levels were found in rats receiving cyclosporine alone and in those given cyclosporine plus GR32191. More than 50% of the animals on cyclosporine alone died from uremia before the end of the observation period. By contrast, rats receiving cyclosporine in combination with GR32191 had a prolonged survival.(ABSTRACT TRUNCATED AT 250 WORDS)
Cryoablation of drug-resistant ventricular tachycardia in a patient with a variant of scleroderma.
Authors: J J Gallagher, R W Anderson, J Kasell, J R Rice, E L Pritchett, H J Gault, L Harrison, A G Wallace
Journal: Circulation (1978)

A 37-year-old man with a benign variant of scleroderma (CRST syndrome: calcinosis circumscripta, Raynaud's phenomenon, sclerodactyly, and telangiectasia) presented with recurrent ventricular tachycardia. Preoperative electrophysiologic study suggested that the mechanism of tachycardia was an ectopic pacemaker focus in the right ventricle. Right ventricular dilatation, tricuspid insufficiency, normal pulmonary pressures, and normal coronary arteries were also demonstrated. At surgery, epicardial mapping localized the site of origin of ventricular tachycardia to the anterior right ventricle near the crista supraventricular. Intramural recordings of the site of tachycardia demonstrated autonomous activity unreflected on the peripheral ECG during brief periods of sinus rhythm. Local epicardial cooling of this area with a cryoprobe promptly terminated ventricular tachycardia with resumption of tachycardia on warming. The focus was ablated by freezing the area at -60 degrees C. The patient remained free of dysrhythmia on no anti-arrhythmic agents for eight months at which time he had a single recurrence of ventricular tachycardia from a different site in the right ventricle. This technique offers a method for ablating sites of dysrhythmia arising in diffusely diseased myocardium.
Lymphatic spread of melanoma mimicking Kaposi-like angiodermatitis
Authors: G. Ferrara, G. Sarracco, A. Erbazzi, G. Argenziano, F. Cusano
Journal: British Journal of Dermatology (2003)

Sir, We describe a highly unusual type of metastatic spread of melanoma to the skin through lymphadenectomy‐impaired lymphatic vessels. These metastatic deposits, when presenting solely with flat (macular) lesions, can simulate Kaposi‐like acroangiodermatitis. A 73‐year‐old woman was seen for progressive enlargement of the left leg and thigh; oedema had been slowly developing for 2 years after inguinal lymphadenectomy for nodal metastasis of acral lentiginous melanoma of the left sole. The primary lesion (Clark level IV; Breslow thickness 3·3 mm; ulcerated) had been excised 3 years before inguinal metastases had been detected. On examination, the involved leg and thigh showed areas of bluish colour with a finely reticular pattern (Fig. 1a). The lesions also showed a brown hue in some areas. The patient reported that the pigmentation had been gradually enlarging for the last month. Skin biopsy showed, within both the superficial and the deep dermis, widened lymphatic spaces filled with highly atypical pigmented cells (Fig. 1b). These cells stained strongly with polyclonal anti‐S100 and antimelanoma HMB‐45 antibodies (Dako, Glostrup, Denmark). A diagnosis of endolymphatic spread of melanoma was made. The patient refused any chemotherapy and was alive with the disease at the last follow‐up examination performed 4 months after the diagnosis of metastatic skin disease.
Allele specificity of structural requirement for peptides bound to HLA-DRB1*0405 and -DRB1*0406 complexes: implication for the HLA-associated susceptibility to methimazole-induced insulin autoimmune syndrome.
Authors: S Matsushita, K Takahashi, M Motoki, K Komoriya, S Ikagawa, Y Nishimura
Journal: The Journal of Experimental Medicine (1994)

Self-peptides bound to HLA-DR4 (DRA-DRB1*0405 complex) were eluted from the purified DR4 complex, fractionated on reverse-phase HPLC, and subjected to NH2-terminal sequencing. Seven independent sequences were obtained, and all putative peptides synthesized bound to DRB1*0405 as well as DRB1*0406 complex, which differ only at DR beta residues 37, 57, 74, and 86. Binding assay using analogue peptides of a DR4 binder GSTVFDNLPNPE revealed that FxxLxN is an important anchor motif necessary for binding (where x is any amino acid), which was common to DRB1*0405 and 0406. Determination of the binding affinity of 60 synthetic AAFAALANAA-based analogue peptides showed that substituting F to W or C; L to F, W, or Y; and N to Q or S on AAFAALANAA changed the affinity substantially between DRB1*0405 and DRB1*0406. It is noteworthy that all patients with methimazole-induced insulin autoimmune syndrome are positive for DRB1*0406 and negative for DRB1*0405. Interestingly, the quantitative structural motif identified in this study predicted that 8TSICSLYQLE17 of human insulin alpha chain may bind specifically to DRB1*0406 using its 10IxxLxQ15 motif. Indeed, DRB1*0406 complex bound 8TSICSLYQLE17 with a high affinity, and in striking contrast, DRB1*0405 complex did not. Furthermore, a short-term T cell line specific to human insulin established from a DRB1*0406-bearing individual did show reactivity with a peptide fragment containing the 10IxxLxQ15 motif. Although this fragment probably exists at a very low level under normal physiological conditions due to the disulfide bond between flanking cysteine residues (6Cys-11Cys), a reducing compound such as methimazole may cleave the disulfide bond in vivo and allow DR alpha-DRB1*0406 complex on antigen-presenting cells to bind much of the linear fragment of insulin alpha chain, which may lead to the activation of self-insulin-specific T-helper cells.
Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: modelling study and economic analysis
Authors: Andrew N Phillips, Valentina Cambiano, Alec Miners, Paul Revill, Deenan Pillay, Jens D Lundgren, Diane Bennett, Elliott Raizes, Fumiyo Nakagawa, Andrea De Luca, Marco Vitoria, Jhoney Barcarolo, Joseph Perriens, Michael R Jordan, Silvia Bertagnolio
Journal: The Lancet HIV (2014)
The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage.
Authors: Cemalettin Bekpen, Julia P Hunn, Christoph Rohde, Iana Parvanova, Libby Guethlein, Diane M Dunn, Eva Glowalla, Maria Leptin, Jonathan C Howard
Journal: Genome biology (2005)

Members of the p47 (immunity-related GTPases (IRG) family) GTPases are essential, interferon-inducible resistance factors in mice that are active against a broad spectrum of important intracellular pathogens. Surprisingly, there are no reports of p47 function in humans.Here we show that the p47 GTPases are represented by 23 genes in the mouse, whereas humans have only a single full-length p47 GTPase and an expressed, truncated presumed pseudo-gene. The human full-length gene is orthologous to an isolated mouse p47 GTPase that carries no interferon-inducible elements in the promoter of either species and is expressed constitutively in the mature testis of both species. Thus, there is no evidence for a p47 GTPase-based resistance system in humans. Dogs have several interferon-inducible p47s, and so the primate lineage that led to humans appears to have lost an ancient function. Multiple p47 GTPases are also present in the zebrafish, but there is only a tandem p47 gene pair in pufferfish.Mice and humans must deploy their immune resources against vacuolar pathogens in radically different ways. This carries significant implications for the use of the mouse as a model of human infectious disease. The absence of the p47 resistance system in humans suggests that possession of this resistance system carries significant costs that, in the primate lineage that led to humans, are not outweighed by the benefits. The origin of the vertebrate p47 system is obscure.
Surgical synovectomy and experimental immune synovitis in the rabbit knee joint.
Authors: H L Currey, C J Moore, A D Prentice
Journal: Annals of the Rheumatic Diseases (1970)

Surgical synovectomy is used regularly in the treatment of rheumatoid arthritis, particularly in the kneejoint.Pain is often relieved by this operation, but the long-term effects upon the progress of the disease in the operated joint are unknown.It is proving extremely difficult to perform the type of controlled clinical trial needed to determine the long-term results.Meanwhile, without a better understanding of the pathogenesis of rheumatoid arthritis, the rationale for this operation remains a matter for speculation.It is not known whether any benefit results from excision of inflammatory tissue, removal of antigen, alteration of blood supply, or other non-specific effects.It seemed that information about this might be obtained from the use of an animal model, and we have therefore studied the influence of surgical synovectomy on immune synovitis induced in the rabbit knee joint.This is probably the smallest animal in which such a procedure is practical, and the pattern of immune synovitis in this joint has been extensively studied by Glynn (1968).1 ml.emulsion contained 10 mg.mixed human serum proteins (HSP).This volume was injected intracutaneously divided between multiple sites on the animal's back, and 3 weeks later the injection was repeated.In the pilot study this regimen was found to produce positive 'delayed' skin tests to 50 ug.HSP in all of the six animals, and to 10 jig. in all but one. INDUCTION OF ARTHRITIS25 mg.HSP made up to 1 ml.with physiological saline was injected into each joint.Strict sterility was observed in the preparation and administration.Eight animals received injections into both knee joints weekly for 3 weeks.Two animals were not injected and served as controls. ANAESTHESIAThis was obtained with a 1:50 solution of bromethol (Avertin) given by intraperitoneal injection in a dose of copyright.
Isometric Time-Tension Relationships as an Index of Myocardial Contractility
Authors: JOHN H. SIEGEL, EDMUND H. SONNENBLICK
Journal: Circulation Research (1963)

The mechanics of isometric contraction in the heart were studied in both isolated papillary muscle and in an innervated, isovolumetric heart in situ. The maximum rate of development of isometric tension (dp/dt) and the integrated isometric tension (IIT), were studied on a beat-to-beat basis. The results indicate: 1) At a given heart rate, both the IIT as well as dp/dt vary directionally as changes in end diastolic volume and fiber length. During isometric contraction, the ratio dp/dt/IIT is independent of changes in fiber length, and remains a constant for any given state of contractility. 2) At a constant heart rate, and at constant volume, cardiac sympathetic nerve stimulation markedly increases dp/dt and IIT. The ratio dp/dt/IIT is elevated to a new constant which is also independent of fiber length. 3) Increasing heart rate increases the ratio dp/dt/IIT. This increase is, however, small compared to the increase in this ratio produced by sympathetic stimulation at the same rate. 4) The effects of heart rate and sympathetic stimulation are additive. 5) Differences have been noted between the manner in which norepinephrine, calcium, and acetyl strophanthidin alter the mechanics of the isovolumetric ventricle. This evaluation of the myocardial contraction is also uninfluenced by the adequacy of ventricular relaxation. 6) Comparison of the isovolumetric ventricle with isolated papillary muscle yielded directly analogous results, indicating that the properties observed were intrinsic to cardiac muscle and are not dependent upon structural arrangements in the intact heart. It is suggested that this ratio dp/dt/IIT is a quantitative measure of the contractility of the myocardium.
DNA Sequence Variation at a Duplicated Gene: Excess of Replacement Polymorphism and Extensive Haplotype Structure in the Drosophila melanogasterbicoid Region
Authors: John F Baines, Ying Chen, Aparup Das, Wolfgang Stephan
Journal: Molecular Biology and Evolution (2002)

The bicoid (bcd) gene of Drosophila has played an important role in understanding the system of developmental regulatory genes that controls segmentation in the fruit fly. Several studies in Drosophila and closely related insects suggest that bcd may be the result of a gene duplication in the Dipteran lineage. In addition, the presence of a large, conserved secondary structure in the 3' untranslated region (UTR) makes the bcd gene a good candidate for studying compensatory evolution and the relationship between RNA secondary structure and patterns of standing variation in natural populations. Despite these interesting aspects, a population-level analysis has until now not been performed on bcd. In this study, DNA sequence variation was examined for a 4-kb region of the bcd gene, including a portion of the 5' UTR, the entire coding region, and the 3' UTR, for 25 Drosophila melanogaster isofemale lines from Zimbabwe and one allele from D. simulans. Statistical tests revealed a significant excess of replacement polymorphisms in the D. melanogaster lineage that are clustered in two putative linker regions of the Bicoid protein. This result is consistent with a relaxation of selective constraints in these regions. In addition, we found a distinct haplotype structure and a significantly smaller number of haplotypes than predicted by the standard neutral model. It is unlikely that the haplotype structure is maintained by epistatic selection acting on the secondary structure in the 3' UTR or by the association of the bcd gene with polymorphic inversions. Instead, our two main observations, namely the occurrence of a haplotype structure and the excess of replacement polymorphisms, may indicate that the selective history of this gene is rather complex, involving both the relaxation of purifying selection in some parts of the protein and the action of positive selection in other parts of the gene region.
Monitoring of Kindreds With Hereditary Predisposition for Cutaneous Melanoma and Dysplastic Nevus Syndrome: Results of a Swedish Preventive Program
Authors: Johan Hansson, Mia Bergenmar, Per-Åke Hofer, Göran Lundell, Eva Månsson-Brahme, Ulrik Ringborg, Ingrid Synnerstad, Annika Ternesten Bratel, Ann-Marie Wennberg, Inger Rosdahl
Journal: Journal of Clinical Oncology (2007)

To evaluate a program initiated in 1987 by the Swedish Melanoma Study Group aiming to provide preventive surveillance to kindreds with hereditary cutaneous melanoma and dysplastic nevus syndrome.Overall, 2,080 individuals belonging to 280 melanoma families were followed for 14 years between 1987 and 2001 at 12 participating centers. Data were registered in a central database.Among 1,912 skin lesions excised during follow-up, 41 melanomas were removed in 32 individuals. Of these, 15 (37%) were in situ melanomas and 26 (63%) invasive melanomas. The median tumor thickness of invasive melanomas was 0.5 mm. Ulceration was absent in 24 of 26 invasive melanomas (92%) and 12 (46%) lacked vertical growth phase. Compared with melanomas in the general Swedish population, the melanomas identified in these kindreds during follow-up had better prognostic characteristics. All melanomas except one were diagnosed in families with two or more first-degree relatives with melanoma. Diagnosis of melanoma occurred in three of eight kindreds with germline CDKN2A mutations, supporting that families with such mutations are at increased risk for melanoma development. Of the 32 individuals who developed melanoma during follow-up, 21 (66%) had had at least one previously diagnosed melanoma.This study shows that a coordinated program aimed at detecting and offering skin surveillance in kindreds with hereditary cutaneous melanoma results in a low incidence of melanomas during the follow-up period and that the tumors that do arise have favorable prognostic characteristics.
What behavioral benefit does stiffness control have? An elaboration of Smith's proposal
Authors: Gerard P. Van Galen, Angelique W. Hendriks, Willem P. DeJong
Journal: Behavioral and Brain Sciences (1996)

It is argued that stiffness is, as Smith assumes, a likely movement-control parameter for the brain, as is supported by the results of several behavioral experiments. However, without further elaboration of what specific type and implementation of stiffness is meant it is perhaps premature to speculate on its possible locus of control, [SMITH]