tbuckley/cabot-search huggingface dataset:
Peak flow variation in childhood asthma: relationship to symptoms, atopy, airways obstruction and hyperresponsiveness. Dutch CNSLD Study Group
Authors: PL Brand, EJ Duiverman, DS Postma, HJ Waalkens, KF Kerrebijn, EE van Essen-Zandvliet
Journal: European Respiratory Journal (1997)

Although home recording of peak expiratory flow (PEF) is considered useful in managing asthma, little is known about the relationship of PEF variation to other indicators of disease activity. We examined the relationship of PEF variation, expressed in various ways, to symptoms, atopy, level of lung function, and airways hyperresponsiveness in schoolchildren with asthma. One hundred and two asthmatic children (aged 7-14 yrs) recorded symptoms and PEF (twice daily) in a diary for 2 weeks after withdrawal of all anti-inflammatory maintenance medication. PEF variation was expressed as amplitude % mean, as standard deviation and coefficient of variation of all recordings, and as low % best (lowest PEF as percentage of the highest of all values). Atopy and level of forced expiratory volume in one second (FEV1) % predicted were not significantly related to PEF variation. The provocative dose of histamine causing a 20% fall in FEV1 (PD20) and symptom scores were significantly, but weakly, related to PEF variation. The index, low % best, proved easy to calculate and effective in identifying a short-term episode of reduced PEF. We conclude that peak expiratory flow variation in children with stable, moderately severe asthma is significantly, but weakly, related to symptoms and airways hyperresponsiveness. These three phenomena, therefore, all provide different information on the actual disease state. Expressing peak expiratory flow variation as low % best is easy to perform and appears to be clinically relevant.
Low Thyroid Function Leads to Cardiac Atrophy With Chamber Dilatation, Impaired Myocardial Blood Flow, Loss of Arterioles, and Severe Systolic Dysfunction
Authors: Yi-Da Tang, James A. Kuzman, Suleman Said, Brent E. Anderson, Xuejun Wang, A. Martin Gerdes
Journal: Circulation (2005)

Although thyroid dysfunction has been linked to heart failure, it is not clear whether hypothyroidism alone can cause heart failure.Hypothyroidism was induced in adult rats by treatment with 0.025% propylthiouracil (PTU) for 6 weeks (PTU-S) and 1 year (PTU-L). Echocardiographic measurements, left ventricular (LV) hemodynamics, isolated myocyte length (KOH method), myocardial blood flow (fluorescent microspheres), arteriolar morphometry, and gene expression (Western blot) were determined. Heart weight, heart rate, LV systolic blood pressure, LV ejection fraction, LV fractional shortening, and systolic wall thickness were reduced in PTU-S and PTU-L rats. LV internal diameter in systole increased by 40% in PTU-S and 86% in PTU-L. LV internal dimension in diastole was increased in PTU-S and PTU-L rats, but only PTU-L rats showed a significant increase in myocyte length due to series sarcomere addition. Resting and maximum (adenosine) myocardial blood flow were reduced in both PTU-S and PTU-L rats. Impaired blood flow was due to a large reduction in arteriolar length density and small arterioles in PTU-S and PTU-L (P<0.05 or greater for all of the above comparisons). Expression of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)-2a and alpha-myosin heavy chain were reduced in hypothyroidism, whereas phospholamban and beta-myosin heavy chain were increased.Hypothyroidism led to severe, progressive systolic dysfunction and increased chamber diameter/wall thickness ratio despite a reduction in cardiac mass. Chamber dilatation in PTU-L rats was due to series sarcomere addition, typical of heart failure. Hypothyroidism resulted in impaired myocardial blood flow due to a dramatic loss of arterioles. Thus, we have identified 2 important new mechanisms by which low thyroid function may lead to heart failure.
Estimates of Insulin Sensitivity Using Glucose and C-Peptide From the Hyperglycemia and Adverse Pregnancy Outcome Glucose Tolerance Test
Authors: Tatjana Radaelli, Kristen Anne Farrell, Larraine Huston-Presley, Saeid Baradaran Amini, John Patrick Kirwan, Harold David McIntyre, Patrick Michael Catalano
Journal: Diabetes Care (2009)

OBJECTIVE To determine if glucose and C-peptide values obtained as part of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study could be used to estimate insulin sensitivity during late pregnancy. RESEARCH DESIGN AND METHODS A total of 78 women enrolled in the HAPO study were recruited for this ancillary study. Venous plasma samples were drawn after an 8- to 10-h fast (time 0) and at 30, 60, 90, and 120 min after a 75-g glucose challenge, which was performed at 24–32 weeks' gestation. Samples were analyzed for plasma glucose, insulin, and C-peptide. Insulin sensitivity was estimated using the established Matsuda and DeFronzo insulin sensitivity index for oral glucose tolerance tests (ISOGTT). Insulin sensitivity was also calculated from two other commonly used indexes of insulin sensitivity (that for homeostasis model assessment [ISHOMA] and that for quantitative insulin sensitivity check index [ISQUICKI]). A new insulin sensitivity index was calculated using the glucose and C-peptide concentrations at 0 and 60 min to derive ISHOMA C-pep, ISQUICKI C-pep, and ISOGTT C-pep. These indexes were then correlated with insulin sensitivity estimated from the ISOGTT. RESULTS The strongest correlation with the ISOGTT was obtained for ISOGTT C-pep (r = 0.792, P &amp;lt; 0.001). Further, the correlations of ISHOMA C-pep and ISQUICKI C-pep with ISOGTT were also significant (r = 0.676, P &amp;lt; 0.001 and r = 0.707, P &amp;lt; 0.001, respectively). CONCLUSIONS These data suggest that calculated ISOGTT C-pep is an excellent predictor of insulin sensitivity in pregnancy and can be used to estimate insulin sensitivity in over 25,000 women participating in the HAPO study.
Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis
Authors: Vissia Viglietta, Clare Baecher-Allan, Howard L. Weiner, David A. Hafler
Journal: The Journal of Experimental Medicine (2004)

CD4+CD25+ regulatory T cells contribute to the maintenance of peripheral tolerance by active suppression because their deletion causes spontaneous autoimmune diseases in mice. Human CD4+ regulatory T cells expressing high levels of CD25 are suppressive in vitro and mimic the activity of murine CD4+CD25+ regulatory T cells. Multiple sclerosis (MS) is an inflammatory disease thought to be mediated by T cells recognizing myelin protein peptides. We hypothesized that altered functions of CD4+CD25hi regulatory T cells play a role in the breakdown of immunologic self-tolerance in patients with MS. Here, we report a significant decrease in the effector function of CD4+CD25hi regulatory T cells from peripheral blood of patients with MS as compared with healthy donors. Differences were also apparent in single cell cloning experiments in which the cloning frequency of CD4+CD25hi T cells was significantly reduced in patients as compared with normal controls. These data are the first to demonstrate alterations of CD4+CD25hi regulatory T cell function in patients with MS.
Identification of a serum-detectable metabolomic fingerprint potentially correlated with the presence of micrometastatic disease in early breast cancer patients at varying risks of disease relapse by traditional prognostic methods
Authors: C. Oakman, L. Tenori, W.M. Claudino, S. Cappadona, S. Nepi, A. Battaglia, P. Bernini, E. Zafarana, E. Saccenti, M. Fornier, P.G. Morris, L. Biganzoli, C. Luchinat, I. Bertini, A. Di Leo
Journal: Annals of Oncology (2011)
Involvement of tachykinin receptors in sensitisation to cow’s milk proteins in guinea pigs
Authors: J Gay, J Fioramonti, R Garcia-Villar, X Emonds-Alt, L Bueno
Journal: Gut (1999)

BACKGROUND There is growing evidence for a pivotal role for tachykinins in gut neuroimmune interactions. AIMS To determine whether NK1, NK2, and NK3 tachykinin receptors are involved in milk protein induced allergic sensitisation. METHODS Eight groups of 12 Dunkin-Hartley guinea pigs (250–300 g) were used. Four groups were sensitised to milk proteins for three weeks. During this period, these animals were injected intraperitoneally each day with NK1 (SR 140333; 0.3 mg/kg), NK2 (SR 48968; 5 mg/kg), or NK3 (SR 142801; 5 mg/kg) receptor antagonist or vehicle. The fifth group had water available instead of milk and was used as a non-sensitised control. The three other groups received the NK receptor antagonists for three weeks but were not sensitised to milk proteins. RESULTS Sensitised animals treated with NK1 and NK3 receptor antagonists had both lower IgE and IgG serum titres, evaluated by passive cutaneous anaphylaxis, and lower specific IgG serum titres, determined by enzyme linked immunosorbent assay (ELISA), than vehicle treated animals. Sensitisation induced an increase in intestinal mast cell number which was abolished by treatment with the NK1 receptor antagonist. Antigenic challenge-induced jejunal hypersecretion was also blocked by treatment with the NK1 receptor antagonist. CONCLUSION In guinea pigs, NK1 and NK3 but not NK2 receptors are involved in sensitisation to cow’s milk. However, NK1 but not NK3 receptor antagonists abolish both the hypermastocytosis induced by food allergy and the hypersecretion induced by antigenic challenge, suggesting different roles for NK1 and NK3 receptors in the mechanisms of sensitisation to β-lactoglobulin.
A1C in Gestational Diabetes Mellitus in Asian Indian Women
Authors: Vijayam Balaji, Balji S. Madhuri, Srinivasan Ashalatha, Suganthi Sheela, Suresh S, Veerasamy Seshiah
Journal: Diabetes Care (2007)

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance of varying degrees of severity with onset or first recognition during pregnancy. The current recommendation is to perform screening test between 24 and 26 weeks of gestation, although there are reports claiming that between 40 and 66% of women with GDM could be detected during early pregnancy (1,2). The policy of screening in the third trimester has resulted in a significant number of pregnant women delivering big babies, despite good glycemic control (3), whereas an early screening for glucose intolerance and care has resulted in the reduction of some of the hyperglycemia-related complications (4). Pregnant women diagnosed as having glucose intolerance in the first trimester are likely to have unrecognized type 2 diabetes before pregnancy (pre-GDM) or pregnancy-induced glucose intolerance during pregnancy (GDM) (5,6). These two clinical situations need to be delineated, as pre-GDM women are likely to have more morbidity and require immediate attention. Hence, we undertook this study to find out whether estimation of A1C levels, along with oral glucose tolerance tests (OGTTs), would help us to distinguish between these two groups, as A1C is directly related to the average concentration of blood glucose in the previous weeks. We also wanted to assess the A1C level during normal pregnancy in our population.

We screened 507 consecutive pregnant women for diabetes and pregnancy who were attending our referral center, irrespective of trimesters, with a 75-g OGTT. Women with a history of type 2 diabetes and GDM were excluded from this study. Blood samples were drawn at fasting and at 1 and 2 h for estimating plasma glucose. The plasma glucose …
Assessment of xanthine oxidase in human lung and lung transplantation
Authors: VL Kinnula, A Sarnesto, L Heikkila, H Toivonen, S Mattila, KO Raivio
Journal: European Respiratory Journal (1997)

Oxygen free radical generation by xanthine oxidase (XO) is a possible mechanism in the injury following reperfusion of transplanted organs. This study was undertaken to investigate XO in human lung, and to investigate whether XO is released into the blood stream during the immediate postoperative period after lung transplantation. XO activity was measured in healthy human lung tissue, and XO protein and the adenine nucleotide catabolic products hypoxanthine, xanthine and uric acid were analysed in the plasma samples collected during human heart-lung transplantation (n=4), double lung transplantation (n=2), and single lung transplantation (n=1). Neutrophil degranulation was assessed by plasma lactoferrin measurements. The results indicated that XO activity (detection limit 5 pmol x min(-1) x mg(-1) protein) and protein (detection limit 5 ng x mg-1 protein) were undetectable in the lungs of five healthy individuals. Similarly, no XO protein could be found in the plasma samples from the right ventricle or left atrium during and after the transplantation in any of the cases. Plasma xanthine and hypoxanthine concentrations were elevated 2-10 fold immediately after the reperfusion of the transplant, indicating washout of high-energy phosphate degradation products from the ischaemic lung. Plasma uric acid decreased rather than increased immediately after the surgery and during the following 24 h. Lactoferrin was elevated during the surgery. In conclusion, these results show that XO activity in human lung is low, it is not released into the blood stream during human heart-lung transplantation, and it is unlikely to contribute to postoperative complications in these patients.
Epinephrine in the Heart
Authors: Thomas W. Lameris, Sandra de Zeeuw, Dirk J. Duncker, Wouter Tietge, Gooitzen Alberts, Frans Boomsma, Pieter D. Verdouw, Anton H. van den Meiracker
Journal: Circulation (2002)

Background— Several studies have suggested that epinephrine augments the release of norepinephrine from sympathetic nerve terminals through stimulation of presynaptic receptors, but evidence pertaining to this mechanism in the heart is scarce and conflicting. Using the microdialysis technique in the porcine heart, we investigated whether epinephrine, taken up by and released from cardiac sympathetic nerves, can increase norepinephrine concentrations in myocardial interstitial fluid (NE MIF ) under basal conditions and during sympathetic activation. Methods and Results— During intracoronary epinephrine infusion of 10, 50, and 100 ng/kg per minute under basal conditions, large increments in interstitial (from 0.31±0.05 up to 140±30 nmol/L) and coronary venous (from 0.16±0.08 up to 228±39 nmol/L) epinephrine concentrations were found, but NE MIF did not change. Left stellate ganglion stimulation increased NE MIF from 3.4±0.5 to 8.2±1.5 nmol/L, but again, this increase was not enhanced by concomitant intracoronary epinephrine infusion. Intracoronary infusion of tyramine resulted in a negligible increase in epinephrine concentration in myocardial interstitial fluid (EPI MIF ), whereas 30 minutes after infusion of epinephrine an increase of 9.5 nmol/L in EPI MIF was observed, indicating that epinephrine is taken up by and released from cardiac sympathetic neurons. Although 68% to 78% of infused epinephrine was extracted over the heart, the ratio of interstitial to arterial epinephrine concentrations was only ≈20%, increasing to 29% with neuronal reuptake inhibition. Conclusions— Our findings demonstrate epinephrine release from cardiac sympathetic neurons, but they do not provide evidence that epinephrine augments cardiac sympathoneural norepinephrine release under basal conditions or during sympathetic activation.
Physiologic and Immunologic Hurdles to Xenotransplantation
Authors: BENJAMIN SAMSTEIN, JEFFREY L. PLATT
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The major problem in the field of renal transplantation is currently the shortage of available kidneys. However, the use of animals as a source of kidneys, i.e. , xenotransplantation, is increasingly being viewed as a potential solution to this problem. One preeminent hurdle to xenotransplantation is the immune response of the recipient against the graft; other hurdles include the physiologic limitations of the transplant, infection, and ethical considerations. This review summarizes what is currently known regarding the obstacles to xenotransplantation and some potential solutions to those problems.
BRAIN TO BRAIN TRANSMISSION OF THE SUBMAXILLARY GLAND VIRUS IN YOUNG GUINEA PIGS
Authors: N. Paul Hudson, Floyd S. Markham
Journal: The Journal of Experimental Medicine (1932)

The submaxillary gland virus of guinea pigs was serially transmitted from brain to brain in young guinea pigs. The source of virus was the submaxillary glands of six groups of stock animals. Brain to brain transfer was effected in two series, in one to the second generation and in the other to the third. The transmission was evidenced by the presence of nervous symptoms and death and by a typical microscopic pathology of the brain. Only certain attempts were successful, ten of twenty-three brain to brain injections being fatal with the specific histopathology present in five. A few observations suggest that the virus may be present spontaneously in the gland and experimentally in the brain without cellular changes being demonstrable, or before they are evident. While we were able to transmit the virus from brain to brain with fatal results by single injections of small doses, this was not readily accomplished and the transmission failed after two or three passages. We were unable to show any perceptible increase in virulence or adaptation of the virus to the brain tissue of the natural host. The histopathology was that of a meningoencephalitis. The inflammatory reaction irregularly involved the meninges, the underlying brain substance, and the perivascular tissue of the meninges and upper cortical layer. These structures were infiltrated with mononuclear cells, many of which contained a typical acidophilic inclusion. Congestion of cerebral capillaries uniformly occurred and various degrees of recent hemorrhage were frequently found. Necrosis was noted only when associated with an occasional area of extensive hemorrhage. Similar changes were observed in sections of the spinal cord. When sufficient time (15 days or more) elapsed between cerebral inoculation and death, typical cellular inclusions were seen in the salivary glands, whereas none was found in animals that died earlier (7 to 9 days). Under the first mentioned conditions, inclusions were demonstrated in the parotid and mucous portion of the submaxillary glands, although in spontaneously infected animals, we failed to find the mucous portion involved and other workers report that the parotid is spared. About one-third of the stock guinea pigs examined showed cellular inclusions in both the nucleus and cytoplasm of epithelial duct cells of the serous part of the submaxillary gland. From an analysis of the results of brain to brain inoculations, it was evident that spontaneous infection and resistance to cerebral inoculation increased with age. The 3rd week of life is the period of choice for such experimentation.
Characteristics of Patients with Asthma Within a Large HMO
Authors: MOLLY L. OSBORNE, WILLIAM M. VOLLMER, KATHRYN L. P. LINTON, A. SONIA BUIST
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Adequate information about characteristics of asthmatic patients in large health maintenance organizations (HMOs) is still lacking. As part of an ongoing longitudinal study, baseline data were collected on 914 individuals aged 3 to 55 yr with physician-diagnosed asthma within a large HMO, Kaiser Permanente, NW Region. There were no significant differences between men and women in post-bronchodilator FEV1 when expressed as percent (%) predicted yet women with asthma reported more daytime and nocturnal symptoms than men (p = 0.002), and worse quality of life in all but three of 14 subscales in two asthma quality of life instruments. Specifically, women in the 35–55 yr age group uniformly reported worse physical functioning on the SF-36 quality of life scale (71 ± 23 versus 85 ± 18; p = 0.001), social functioning (73 ± 21 versus 77 ± 20; p = 0.016), and bodily pain (63 ± 27 versus 72 ± 24; p < 0.001). Also these women reported use of more health care (p = 0.002) and more medications for asthma than men (p < 0.01). Our data suggest that men and women respond differently to their asthma, and observed gender differences in various measures of asthma such as hospital admissions, quality of life, and use of metered dose inhalers (MDIs), may be related to this difference in response to disease, rather than to real differences in the disease between men and women. Understanding gender related differences in response to a chronic disease such as asthma is important in tailoring an education and management plan to each individual patient.
Early atherosclerosis in humans: role of diffuse intimal thickening and extracellular matrix proteoglycans
Authors: Y. Nakashima, T. N. Wight, K. Sueishi
Journal: Cardiovascular Research (2008)

This review attempts to define the early events that lead to lesions of human atherosclerosis based on careful morphological studies in human autopsy specimens. In contrast to most small laboratory animals, diffuse intimal thickening (DIT) is present in human arteries before atherosclerosis develops, particularly in the atherosclerosis-prone arteries such as coronary arteries and abdominal aorta. In the earliest stage of atherosclerosis, lipids deposit eccentrically in the deep layer of DIT to form Type I lesions. These layers are enriched in extracellular matrix (ECM) proteoglycans such as biglycan. Following lipid deposition, macrophages appear in these regions and foam cells are observed (Type II lesions). Such observations support the 'response-to-retention' hypothesis that states that a principle early event in the pathogenesis of human atherosclerosis is the trapping and retention of lipoproteins by ECM proteoglycans followed by infiltration and accumulation of macrophages.
Synergistic Antitumor Activity of Taxol and Immunotoxin SS1P in Tumor-Bearing Mice
Authors: YuJian Zhang, Laiman Xiang, Raffit Hassan, Chang H. Paik, Jorge A. Carrasquillo, Beom-su Jang, Nhat Le, Mitchell Ho, Ira Pastan
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To investigate the combined antitumor activity in mice of immunotoxin SS1P and Taxol. Methods: Immunodeficient mice were implanted with A431/K5 tumors expressing mesothelin. Established tumors were treated i.v. with immunotoxin SS1P alone, i.p. with Taxol alone, or with the two agents together. SS1P was radiolabeled with 111In and used to study the effect of Taxol on its uptake by A431/K5 tumors. Results: Using doses at which either agent alone caused stabilization of tumor growth, the combination was synergistic causing long-lasting complete remissions in many animals. In contrast, synergy was not observed when the same cells were treated with these agents in vitro. Tumor uptake of 111In-SS1P was not affected by treatment with Taxol. Conclusion: The combination of Taxol and SS1P exerts a synergistic antitumor effect in animals but not in cell culture. This effect is not secondary to increased tumor uptake of the immunotoxin. Synergy could be due to improved immunotoxin distribution within the tumor or could involve factors released by other cell types in the tumors.