tbuckley/cabot-search huggingface dataset:
Factors Affecting the Filling of the Frog's Ventricle After Isotonic Contraction
Authors: RICHARD A. HENNACY, ERIC OGDEN
Journal: Circulation Research (1960)

A measurable factor determining the filling of the heart is the opposition that the myocardium offers to being stretched. This is expressed as "renitence," which is the ratio of filling pressure to the rate of inflow. Isolated frog ventricle was connected to a vessel containing Ringer's solution at a fixed head of pressure. Change in the volume of the heart was recorded optically. From these time-volume curves, renitence was calculated. For the frog ventricle filling and emptying against a fixed head of pressure, the renitence during the filling period first decreases, passes through a minimum, and then increases. The minimum and average renitences occurring during a cycle appeared to be increased by cooling, a rise in filling pressure, pentobarbital or a combination of hypoxia and acidity. The renitence early during the filling cycle is largely determined by the residual tension from the previous systole, and the subsequent increase seems to be determined by the elastic properties of the myocardium.
Intact Proinsulin, des 31,32 Proinsulin, and Specific Insulin Concentrations Among Nondiabetic and Diabetic Subjects in Populations at Varying Risk of Type 2 Diabetes
Authors: Dinesh K Nagi, William C Knowler, Vidya Mohamed-Ali, Peter H Bennett, John S Yudkin
Journal: Diabetes Care (1998)

OBJECTIVE To examine hyperinsulinemia, insulin secretion, and β-cell function in Pima Indians, South Asians, and whites, populations at varying risk of diabetes. RESEARCH DESIGN AND METHODS We investigated 136 Pima Indian, 98 Asian, and 80 white nondiabetic and 172 Pima Indian, 40 Asian, and 49 white diabetic subjects. Highly specific assays for insulin, intact proinsulin, and des 31,32 proinsulin were used. Insulin secretion was assessed using ratio of increment (0 to 30 min) in insulin to glucose concentrations during an oral glucose tolerance test (OGTT). RESULTS Nondiabetic Pima Indians were significantly more obese than Asians and whites. Pima Indian subjects had significantly higher (P &amp;lt; 0.01) fasting insulin concentrations (median 109 pmol/l, range 40−250) than Asian (37 pmol/l, range 17−91) and white (30 pmol/l, range 10−82) subjects. These differences remained significant when controlled for obesity. Nondiabetic Pima Indians also had higher fasting C-peptide concentrations and higher early insulin secretion during an OGTT. Fasting concentrations of intact proinsulin and des 31,32 proinsulin were also significantly higher in Pima Indians (P &amp;lt; 0.01). However, the proportion of proinsulin-like molecules was significantly lower (P &amp;lt; 0.01) in Pima Indians (median 7.9% vs. 12.7% for South Asians and 12.2% for whites). Subjects with diabetes from the three ethnic groups showed significantly higher fasting insulin concentrations but lower 30-min insulin and lower ratios of increment (0−30 min) in insulin to glucose concentrations than did nondiabetic subjects. The proportion of proinsulin-like molecules was not significantly different in diabetic subjects from the three ethnic groups. CONCLUSIONS These specific assays for insulin indicate that after adjusting for obesity nondiabetic Pima Indians are truly hyperinsulinemic, which is consistent with their insulin resistance as measured by other methods. Hyperinsulinemia in this population with a high risk of diabetes is likely to be due to enhanced insulin secretion. Furthermore, in Pima Indians, the predominant β-cell secretory product is insulin and not its precursors. We conclude that the differences in the risk of diabetes among these three groups are not due to differences in insulin secretion or insulin processing. Subjects with type 2 diabetes have defective early insulin secretion during OGTTs but show fasting hyperinsulinemia even when specific assays for insulin are used.
Allele-Specific Loss in Chromosome 9p Loci in Preneoplastic Lesions Accompanying Non-Small-Cell Lung Cancers
Authors: Y. Kishimoto, K. Sugio, J. Y. Hung, A. K. Virmani, D. D. Mclntire, J. D. Minna, A. F. Gazdar
Journal: JNCI Journal of the National Cancer Institute (1995)

Background : Carcinogenesis is a multistep process, which may begin as a consequence of chromosomal changes. Deletions in the short arm of chromosome 9 (9p) have been observed in lung carcinomas. In addition, morphologically recognizable preneoplastic lesions, frequently multiple in number, precede onset of invasive carcinomas. Purpose: We tested for deletions and loss of heterozygosity (LOH) at 9p loci in preneoplastic and neoplastic foci in lungs of patients with non-small-cell lung carcinomas (NSCLCs). Methods : Seven archival, paraffin-embedded, surgically resected NSCLC specimens were selected. They were predominantly from patients with adenocarcinomas and contained multiple preneoplastic lesions, including hyperplasia, metaplasia, dysplasia, and carcinoma in situ (CIS). Fifty-three histologi-cally identified preneoplastic and malignant lesions present in bronchi, bronchioles, and alveoli were precisely microdis-sected from stained tissue sections with a micromanipulator. Stromal lymphocytes were used to determine constitutional heterozygosity. The specimens were analyzed for LOH using polymerase chain reaction-based assays for polymorphism in dinucleotide repeats (microsatellite markers) in interferon alfa (IFNA) and D9S171 loci on 9p. Results : All seven cases were constitutionally heterozygous for one or both microsatellite markers. Five of seven cases had LOH at one or both 9p loci in the invasive primary cancers (doubly informative cases). Four of these five cases also revealed LOH in preneoplastic foci. In the doubly informative cases, LOH was detected in five (38%) of 13 foci of hyperplasia, four (80%) of five foci of dysplasia, and three (100%) of three CIS lesions. LOH was detected in preneoplastic lesions from all regions of the respiratory tract, including bronchi, bronchioles, and alveoli, and involved five different cell types. The identical allele was lost from both the preneoplastic lesions and the corresponding tumors (12 of 12 lesions, 17 of 17 comparisons), a phenomenon we have referred to as "allele-specific mutation." Statistical analyses employing a cumulative binomial test demonstrated that the probabilities of such findings occurring by chance are 2.4 × 10 −4 and 7.6 × 10 −6 , respectively. From comparisons with the previously published data on other chromosomal abnormalities in the same tissue specimens, it appears that LOH at 3p and 9p loci occurred early in the hyperplasia stage, but the ras gene point mutations were relatively late, at the CIS stage. Conclusions : LOH at 9p loci occurs at the earliest stage in the pathogenesis of lung cancer and involves all regions of the respiratory tract. LOH in NSCLC is not random but targets a specific allele in individuals. Studying preneoplastic lesions may help identify intermediate markers for risk assessment and chemoprevention. [J Natl Cancer Inst 87: 1224–1229, 1995]
Navigating in a three-dimensional world
Authors: Kathryn J. Jeffery, Aleksandar Jovalekic, Madeleine Verriotis, Robin Hayman
Journal: Behavioral and Brain Sciences (2013)

Abstract The study of spatial cognition has provided considerable insight into how animals (including humans) navigate on the horizontal plane. However, the real world is three-dimensional, having a complex topography including both horizontal and vertical features, which presents additional challenges for representation and navigation. The present article reviews the emerging behavioral and neurobiological literature on spatial cognition in non-horizontal environments. We suggest that three-dimensional spaces are represented in a quasi-planar fashion, with space in the plane of locomotion being computed separately and represented differently from space in the orthogonal axis – a representational structure we have termed “bicoded.” We argue that the mammalian spatial representation in surface-travelling animals comprises a mosaic of these locally planar fragments, rather than a fully integrated volumetric map. More generally, this may be true even for species that can move freely in all three dimensions, such as birds and fish. We outline the evidence supporting this view, together with the adaptive advantages of such a scheme.
Aspects of audit. 1. The background.
Authors: C D Shaw
Journal: BMJ (1980)

Methods of reviewing health care already exist in Britain, but the debate continues about how practical and acceptable such a review is. The many different terms used to describe review only confuse the issue. "Audit" is a useful term for describing the review of medical work by medical people. This can be divided into "internal audit," or peer review, and "external audit"--that is, review by organisations outside hospital and general practice. The concepts of internal and external audit have a great impact upon the attitudes held by the medical profession about audit. The shortcomings of audit by the professional standards review organisations in the United States are not inevitable in Britian.
Wenckebach Periods and His-Purkinje Conduction
Authors: M. SUSANA HALPERN, GERARDO J. NAU, RAUL J. LEVI, MARCELO V. ELIZARI, MAURICIO B. ROSENBAUM
Journal: Circulation (1974)

Wenckebach periods during sinus rhythm, 2:1 block at a paced rate of 130/min (fig.LA), and AW at a paced rate of 140/mmin (fig.LB).These conduction abnor- malities were all localized proximal to the His bundle recording site, and reversed with atropine administration.Thus, our case appears to be an example of A-V nodal AW in a patient with bifascicular block.4) The ability to provoke AW by surgical traurna to the His- Purkinje system does not mean that such AW could not also be provoked by experimentally induced A-V nodal dysfunction.We would suggest that A-V nodal AW may be as common as AW in the HPS.We would also predict that some episodes of AV in patients with bifascicular block will reflect 2:1 block proximal to the His bundle (A-V nodal) with Wenckebach periods in the remain- ing functioning fascicle.His bundle recordings in pa- tients with AW should help clarify the site or sites of this interesting phenomenon.
Salicylate effects on a monolayer culture of gastric mucous cells from adult rats.
Authors: S Ota, M Razandi, S Sekhon, W J Krause, A Terano, H Hiraishi, K J Ivey
Journal: Gut (1988)

Aspirin, acetyl salicylic acid, damages gastric mucosal cells. This effect is considered related to its inhibition of prostaglandin synthesis. On the other hand, sodium salicylate has been reported to be cytoprotective against drug damage to gastric mucosa in vivo. One reason for this difference is that salicylic acid, unlike acetyl salicylic acid does not inhibit prostaglandin synthesis by gastric mucosa in vivo. Previous studies on tissue culture cells from our laboratory have required gastric mucosa from fetal rats; this was time consuming and expensive. The purpose of this study was to develop a primary cell culture of adult rat fundic epithelial cells and to test the effect of sodium salicylate on: (1) prostaglandin (PGE2) production, (2) cell viability, (3) reducing cell damage by sodium taurocholate. Gastric epithelial cells were isolated from adult rat stomachs and cultured on collagen gel. Cells reached confluency on day 4 at which stage fibroblasts were rarely seen (less than 1%). Autoradiographic study showed that cultured cells incorporated [3-H] thymidine into nuclei. In histochemical studies, 94% of the cells contained PAS positive granules (mucous cells). Mucous granules were observed in the cytoplasm of the majority of cells by electronmicroscopy. These cells synthesised prostaglandin E2 as determined by radioimmunoassay. Indomethacin 10(-4) M strongly suppressed PGE2 production after 30 minutes while 10(-3) and 10(-4)M sodium salicylate had no effect. Pharmacologic concentrations of 10 mM sodium salicylate had no effect on PGE2 production at 30 minutes and only weakly inhibited production after one hour incubation. Sodium salicylate up to 30 mM had no effect on cell viability, a concentration of 50 mM being necessary to produce significant cell damage. Sodium salicylate 10 mM significantly protected cells against damage induced by 10 mM sodium taurocholate. We conclude: (i) adult rat gastric mucous epithelial cells can be successfully cultured in vitro; (ii) prostaglandin synthesis is inhibited by indomethacin but not by low doses of sodium salicylate; (iii) sodium salicylate does not damage gastric mucosal cells except at very high concentrations; (iv) sodium salicylate protects against damage to cells induced by sodium taurocholate.
A monoclonal antibody to von Willebrand factor (vWF) inhibits factor VIII binding. Localization of its antigenic determinant to a nonadecapeptide at the amino terminus of the mature vWF polypeptide.
Authors: W F Bahou, D Ginsburg, R Sikkink, R Litwiller, D N Fass
Journal: Journal of Clinical Investigation (1989)

vWF is a multimeric glycoprotein that serves as the major carrier in plasma of Factor VIII (FVIII). We have used an anti-human vWF MAb W5-6A to investigate the FVIII binding site on vWF. W5-6A inhibited FVIII binding to vWF-coated polystyrene tubes in a concentration-dependent manner with 90% inhibition of FVIII binding at a concentration of 10 micrograms/ml. The W5-6A epitope was identified by screening a vWF fragment library using the bacteriophage expression vector lambda gt11. DNA sequence analysis of 29 immunoreactive phage clones localized the W5-6A epitope to a nonadecapeptide spanning amino acid residues threonine 78 to threonine 96 at the amino-terminus of the mature vWF polypeptide. Purified beta-galactosidase/vWF fusion protein from one of these clones, vWF9, was incubated with radiolabeled W5-6A and caused near complete inhibition of W5-6A binding to vWF. Inhibitory activity was lost after vWF9 trypsinization or reduction and alkylation. These data indicate that (a) the antigenic determinant recognized by W5-6A localizes to a nonadecapeptide at the NH2 terminus of the mature vWF polypeptide, (b) disulfide bonds within vWF9 may be necessary to maintain the structure required for immunoreactivity with W5-6A, and (c) W5-6A recognizes an immunogenic region on vWF that may be at (or near) the major FVIII binding domain.
Re: Luis Felipe Brandao, Riccardo Autorino, Humberto Laydner, et al. Robotic Versus Laparoscopic Adrenalectomy: A Systematic Review and Meta-analysis. Eur Urol 2014;65:1154–61
Authors: Konstantinos P. Economopoulos, Aliki Stamou, Theodoros N. Sergentanis
Journal: European Urology (2014)
"He never got over losing his job": death on the dole.
Authors: R Smith
Journal: BMJ (1985)

Findings on palpation are not always a guide to the true functional findings and the cause of hyperthyroidism. Our results supported this, with only 40 out of 63 cases being correctly diagnosed before the thyroid scan was obtained. Early diagnosis is particularly important in view of the excellent results achieved with radioiodine. Recent follow up studies (paper in preparation) of treatment of single hyperfunctioning nodules have shown that all patients could be rendered euthyroid, in most cases with only one dose of radioiodine, with no incidence of hypothyroidism in patients followed up for up to 10 years.3 We conclude that thyroid scanning is essential in the management of hyperthyroid patients who do not show the classical features of Graves' disease, especially when a nodule or a multinodular goitre is palpated and when no goitre is palpable. This would permit early and successful treatment of single and multiple hyperfunctioning nodules. We thank Susan Finer and Susan Ellam for database assistance and advice and Toni Buckley for typing the manuscript.
Chromosome aberrations and their relevance to metal carcinogenesis.
Authors: H Vainio, M Sorsa
Journal: Environmental Health Perspectives (1981)

Scoring for structural chromosome abnormalities is one of the only practical methods available for detecting visual damage in human genetic material. Cytogenetic tests in vivo and in vitro have shown the clastogenic potential of a number of metals and metal compounds. The difficulties in in vivo studies lie in identifying a specific clastogen in an occupational setting, where simultaneous exposure to a number of organic and inorganic chemicals is a common phenomenon. Metals known to be carcinogens in animals also tend to possess chromosome-damaging properties, even though more extensive studies are needed before any conclusive evidence can be reached. The visible chromosomal damage produced by exposure to metal compounds should be considered as a warning indication of potentially adverse genetic and somatic effects in humans.
The role of polymorphic I-Ak beta chain residues in presentation of a peptide from myelin basic protein.
Authors: C B Davis, J M Buerstedde, D J McKean, P P Jones, H O McDevitt, D C Wraith
Journal: The Journal of Experimental Medicine (1989)

Proteins encoded by genes in the MHC are highly polymorphic. For class II proteins the highest level of polymorphism is found in distinct regions of variability, notably in the membrane-distal domains. To investigate the role of such residues in antigen presentation, we have tested cells transfected with wild-type or mutant I-Ak beta chains for their ability to present the NH2-terminal peptide of myelin basic protein to a panel of T cell clones. We were unable to detect a gross effect on peptide binding, in that all of the mutant cell lines presented antigen to at least one of the cloned T cells. However, the results imply that the more NH2-terminal residues, particularly 12 and 14, are involved in peptide interactions. Mutations at these residues presented antigen only at high antigen concentrations. Furthermore, residues of the more COOH-terminal regions appear to determine TCR interactions. Mutations in the predicted alpha-helical regions of the beta chain affected antigen presentation without abolishing peptide binding.
Linearity of the Frank-Starling relationship in the intact heart: the concept of preload recruitable stroke work.
Authors: D D Glower, J A Spratt, N D Snow, J S Kabas, J W Davis, C O Olsen, G S Tyson, D C Sabiston, J S Rankin
Journal: Circulation (1985)

The Frank-Starling relationship generally has been examined with filling pressure as the index of preload, resulting in a curvilinear function that plateaus at higher filling pressures. To investigate this relationship further in the intact heart, 32 dogs were chronically instrumented with left ventricular and pleural micromanometers and with regional (10 dogs) or global (22 dogs) ultrasonic dimension transducers. Seven days after implantation, left ventricular pressure and regional or global dimensions were recorded in the conscious state. After autonomic blockade, preload was varied by vena caval occlusion. Myocardial function was assessed by calculating regional or global stroke work, and preload was measured as end-diastolic segment length or chamber volume. The relationship between stroke work and either end-diastolic segment length or chamber volume (termed the preload recruitable stroke work relationship) was highly linear in every study (mean r = .97) and could be quantified by a slope (MW) and x-intercept (LW). Previous nonlinear relationships between stroke work and filling pressure seemed to reflect the exponential diastolic pressure-volume curve. Over the physiologic range of systolic arterial pressures produced by infusion of nitroprusside or phenylephrine, no significant change was observed in MW or LW in the normal dog. Calcium infusion increased both regional and global MW by 71 +/- 19% and 65 +/- 9%, respectively (p less than .02), with no significant change in LW. To normalize for ventricular geometry and heart rate, stroke work was computed from circumferential stress-strain data and converted to myocardial power output, which was then plotted against end-diastolic circumferential strain. This relationship also was highly linear, and the slope, Mmp (mW/cm3 of myocardium), is proposed as a potential measure of intrinsic myocardial performance independent of loading, geometry, and heart rate.
Rupture of a Calcified Achilles' Tendon
Authors: Marius C Wick, Michael Rieger
Journal: New England Journal of Medicine (2008)

A 69-year-old man presented at the emergency room with stabbing pain and swelling of the right lower leg on standing up from a seated position. On clinical examination, rupture of the Achilles' tendon was suspected. Plain radiographs showed a complete rupture of a calcified Achilles' tendon (Panels A and B, arrows), which was confirmed by ultrasonography. The patient reported that when he was 13 years of age, his Achilles' tendon was partially cut by a falling cleaver. He traveled from a remote village to the county hospital by public bus, where his Achilles' tendon and skin were sutured at the . . .
Blood rheology in lupus erythematosus.
Authors: E Ernst, A Hein, M Meurer, T Ruzicka
Journal: Annals of the Rheumatic Diseases (1991)

Blood rheology is one of the determinants of perfusion and might therefore have an impact on the thromboembolic complications of lupus erythematosus. This study aimed at defining the flow properties of blood in patients with various types of lupus erythematosus. Results for 51 patients were compared with those for 20 controls matched for sex. The patients were divided into subgroups--chronic discoid, subacute cutaneous, and systemic lupus erythematosus--according to their clinical or laboratory characteristics. Blood and plasma viscosity, packed cell volume, red cell aggregation, and red cell deformability were used as parameters of blood rheology. Blood and plasma viscosity and red cell aggregation were significantly different in patients compared with controls, indicating reduced blood fluidity in lupus erythematosus. There were no marked sex differences. The rheological effects were greater in those with systemic lupus erythematosus than in those with chronic discoid or subacute cutaneous lupus erythematosus. The presence of a positive antinuclear antibody titre or methods of treatment (systemic steroids or retinoids) had no apparent effect on the parameters tested. It is suggested that a complex haemorheological deficit exists in lupus patients.
Regulatory Defect of Glycolysis in Human Lipoma
Authors: J. N. C. Atkinson, D. J. Galton, C. Gilbert
Journal: BMJ (1974)

A metabolic defect has been observed in extracts of lipomata in which citrate fails to inhibit the conversion of glucose-6-phosphate to glyceride-glycerol. Phospho-fructokinase extracted from lipomata was less sensitive to inhibition by citrate than the enzyme of normal adipose tissue. However, maximal rates of lipogenesis (from glucose or palmitate) and lipolysis (stimulated with isoprenaline) in lipomata were similar to those of normal adipose tissue. This work suggests that loss of negative feedback control of regulatory enzymes may be an early feature in the development of neoplasia.
The Jet-Propelled `Dime'
Authors: Martin McGonagle
Journal: JAMA (1984)

<h3>To the Editor.—</h3> Chevalier Jackson<sup>1</sup>wrote the first article on the inhalation of foreign bodies in 1905, and, since that time, an astounding array of objects have been extracted from the respiratory tract. These objects have included food particles, safety pins (both open and closed), buttons, and bony substances. This is a report of a metallic foreign body being jet propelled into the lungs. <h3>Report of a Case.—</h3> A 62-year-old man with a long-standing history of chronic obstructive pulmonary disease was seen in the emergency room, having inhaled a foreign body. The patient, during an episode of bronchospasm, reached into his pocket and took out his Bronkometer (isoetharine mesylate inhalation aerosol), fully assembled. During the inhalation of the aerosol spray, he coughed and spluttered several times and thought he had swallowed something, but he was unsure in this regard. In the emergency room, auscultation of his chest disclosed some mild