tbuckley/cabot-search huggingface dataset:
mRNA expression of iron regulatory genes in β-thalassemia intermedia and β-thalassemia major mouse models
Authors: Orly Weizer-Stern, Konstantin Adamsky, Ninette Amariglio, Eliezer Rachmilewitz, Laura Breda, Stefano Rivella, Gideon Rechavi
Journal: American Journal of Hematology (2006)

β-Thalassemia is an inherited anemia in which synthesis of the hemoglobin β-chain is decreased. The excess unmatched α-globin chains accumulate in the growing erythroid precursors, causing their premature death (ineffective erythropoiesis). Clinical features of β-thalassemia include variably severe anemia and iron accumulation due to increased intestinal iron absorption. The most anemic patients require regular blood transfusions, which exacerbate their iron overload and result in damage to vital organs. The hepatic peptide hepcidin, a key regulator of iron metabolism in mammals, was recently found to be low in the urine of β-thalassemia patients, compared with healthy controls, despite their iron overload. In our work, we measured by RQ-PCR the liver mRNA expression of hepcidin and other iron regulatory genes in β-thalassemia major mouse model (C57Bl/6 Hbbth3/th3), and compared it with β-thalassemia intermedia mouse model (C57Bl/6 Hbbth3/+) and control mice. We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the β-thalassemia mouse models, compared with the control mice. Significant down-regulation of hepcidin expression in β-thalassemia major, despite iron overload, might explain the increased iron absorption typically observed in thalassemia. Am. J. Hematol. 81:479–483, 2006. © 2006 Wiley-Liss, Inc.
Interferons Direct Th2 Cell Reprogramming to Generate a Stable GATA-3+T-bet+ Cell Subset with Combined Th2 and Th1 Cell Functions
Authors: Ahmed N. Hegazy, Michael Peine, Caroline Helmstetter, Isabel Panse, Anja Fröhlich, Andreas Bergthaler, Lukas Flatz, Daniel D. Pinschewer, Andreas Radbruch, Max Löhning
Journal: Immunity (2010)
Potentiation of Apoptosis by Treatment With the Protein Kinase C-Specific Inhibitor Safingol in Mitomycin C-Treated Gastric Cancer Cells
Authors: G. K. Schwartz, A. Haimovitz-Friedman, S. K. Dhupar, D. Ehleiter, P. Maslak, L. Lai, F. Loganzo, D. P. Kelsen, Z. Fuks, A. P. Albino
Journal: JNCI Journal of the National Cancer Institute (1995)

Background: Protein kinase C (PKC) is a family of enzymes that function in processes relevant to carcinogenesis, tumor cell metastasis, and apoptosis. Safingol, an optical isomer (the L-threo enantiomer) of dihydrosphingosine, is a specific inhibitor of PKC and might represent a novel agent for anticancer therapy. Preclinical animal studies show that safingol alone has a minimal effect on tumor cell growth, but combining this compound with convention al chemotherapy agents dramatically potentiates their antitumor effects. It has been suggested that many chemo-therapeutic agents exert their anti-tumor effects by inducing apoptosis. Purpose: We wanted to determine the extent to which safingol, alone or in combination with a standard chemother-apeutic agent (mitomycin C [MMC]), would promote apoptosis in gastric cancer cells in vitro. Furthermore, we investigated whether the induction of apoptosis in the treated cells was affected by their p53 tumor suppressor status or their drug-resistance status. Methods : SK-GT-5 (p53-deficient and MMC-resistant) and MKN-74 (p53 wild-type and MMC-sensitive) gastric cancer cells were exposed to either no drug, safingol (50μ) alone, MMC (5 lig/ml) alone, or a combination of safingol (50/μM) and MMC (5 μg/mL). In some experiments, cells were exposed simultaneously to safingol and the PKC activator, 3-phorbol 12-myris-tate 13-acetate (PMA), prior to treatment with MMC. Apoptosis was measured by two methods: 1) quantitative fluorescence microscopy of nuclear chromatin condensation in cells stained with the dye, bisbenzamide trihydro-chloride (Hoechst-33258), and 2) terminal deoxynucleotidy transferase (TdT) labeling of the 3'-OH ends of DNA fragments produced in apoptotic cells. Results : As determined by quantitative fluorescence microscopy, exposure of SK-GT-5 cells to safingol alone induced apoptosis in 2% ± 1% (mean ± SD) of the cells, and MMC alone increased that level to 18% ± 1%. However, the combination of safingol and MMC induced apoptosis in 39% ± 1% of the cells (P<.001, for the drug combination versus MMC alone). With MKN-74 cells, safingol alone induced apoptosis in 8% ± 3% of the cells, whereas MMC alone induced apoptosis in 40%± 4% of treated cells and the combination of safingol and MMC induced apoptosis in 83% ± 4% of the cells. Similar results were obtained with the TdT assay. Simultaneous exposure of cells to safingol and PMA abrogated the safingol-mediated enhancement of MMC-in-duced apoptosis. Conclusions: The PKC inhibitor safingol enhances the cytotoxic effect of the chemothera-peutic agent MMC in gastric cancer cells by promoting drug-induced apop61 tosis. The induction of apoptosis occurs regardless of the p53 status or the drug-resistance status of the cells. [J Natl Cancer Inst 1995;87:1394–9]
The Relationship of Physical Fitness to Lipid and Lipoprotein(a) Levels in Adolescents With IDDm
Authors: Audrey Austin, Vijay Warty, Janine Janosky, Silva Arslanian
Journal: Diabetes Care (1993)

OBJECTIVE Increased physical activity and physical fitness are recommended therapeutic modalities in addition to insulin and diet in the management of children with IDDM. The aim of this study was to assess the fitness levels of adolescents with IDDM compared with healthy control subjects and to evaluate the relationship between physical fitness and metabolic control. RESEARCH DESIGN AND METHODS We studied 59 patients with IDDM, 28 boys and 31 girls, age 15.6 ± 2.5 yr, duration of diabetes 7.6 ± 3.5 yr, HbA1 10.6 ± 2.1% (mean ± SD), and compared them with 18 healthy, nondiabetic control subjects, 9 boys and 9 girls, matched for age, BMI, and Tanner stage. Physical fitness was measured by VO2max during progressive bicycle ergometry. HbA1 was used to determine glycemic control. Lipid profile included fasting total cholesterol, HDL, LDL, Lp(a), and TG levels. RESULTS Patients with IDDM had lower VO2max levels than control subjects (33.7 ± 7.0 vs. 41.0 ± 10.4 ml · kg−1 · min−1, P = 0.001). Males with IDDM had lower VO2max than male control subjects, but diabetic and control females showed no difference. In IDDM patients, VO2max correlated inversely with HbA1, insulin dose, cholesterol, LDL, TGs, and Lp(a), but did not correlate with HDL, which correlated inversely with BMI. CONCLUSIONS We conclude that the state of physical fitness is an important correlate of lipid levels and Lp(a) in adolescents with IDDM. We speculate that higher physical fitness levels in adolescents with IDDM may decrease the risk of CVD through modulating lipid levels.
Coffee and Coronary Disease
Authors: William B. Kannel, Thomas R. Dawber
Journal: New England Journal of Medicine (1973)

Current assessment of the epidemiology of coronary heart disease indicates a major role of environment in the evolution of this disease. Environmental factors that contribute to the incidence of the disease include dietary habits, cigarette smoking and physical activity. The present issue of the Journal contains an article incriminating coffee drinking as a factor in the development of coronary heart disease. The report of Jick et al. involves a study of coffee consumption by a large number of hospitalized subjects with a discharge diagnosis of myocardial infarction as compared with subjects hospitalized for other reasons. The findings indicate a higher . . .
Altered function and structure of the heart in dogs with chronic elevation in plasma norepinephrine.
Authors: M B Patel, J M Stewart, A V Loud, P Anversa, J Wang, L Fiegel, T H Hintze
Journal: Circulation (1991)

BACKGROUND We have previously shown that chronic elevation of plasma norepinephrine leads to a functional independent increase in left ventricular weight. The goals of the present study were to determine quantitatively the component of the myocardium that accounted for the observed structural changes and to determine the function of the hypertrophied myocardium. METHODS AND RESULTS Mongrel dogs were chronically instrumented for measurement of arterial and left ventricular pressures, left ventricular internal diameter, and left ventricular wall thickness. Subcutaneous osmotic pumps were implanted to release norepinephrine continuously for 28 days. Hemodynamics were measured with dogs in the quietly resting state and during infusions of isoproterenol at 0.1 and 0.5 micrograms/kg/min before and on days 14 and 28 during the infusion of norepinephrine. The hemodynamic response to 10 micrograms/kg phenylephrine, given as a bolus, was also assessed before norepinephrine and 28 days during the infusion of norepinephrine, and the end-systolic pressure-diameter or wall-stress-diameter relations were calculated. On day 28, hearts were arrested in diastole and perfusion fixed in situ. Tissue samples were prepared for electron microscopy and morphometry. Hemodynamic studies showed that isoproterenol (0.5 micrograms/kg/min) reduced mean arterial pressure (MAP) to the same point on each experimental day, and the increases in indexes of contractility were reduced during norepinephrine infusion. Left ventricular dP/dtmax increased 131 +/- 24% on control day, only 67 +/- 20% on day 14, and 55 +/- 18% on day 28. Similar changes were observed in dP/dt/DP40 and dP/dt/end-diastolic circumference. However, Emax, the slope of the end-systolic pressure-diameter or wall stress diameter relations, was unchanged, suggesting that inotropic state was not altered. Morphometric studies showed that the cross-sectional area of myocytes increased by 55%, but myocyte and capillary densities decreased by 34% and 29%, respectively (p less than 0.05) in dogs with high norepinephrine levels. There were no differences in volume fractions of myocytes, capillary lumen, or interstitium or capillary-to-myocyte ratio. CONCLUSIONS The myocardium of dogs with high norepinephrine levels shows reduced inotropic response to beta-adrenergic stimulation despite the increases in left ventricular mass and left ventricular wall thickness, which are a result of growth of the cardiac myocytes and characteristic of concentric hypertrophy. These data suggest that chronic adrenergic stimulation of the heart reduces the beta-receptor coupling to the contractile response without importantly compromising left ventricular function.
THE STUDY AND TEACHING OF OBSTETRICS.
Authors: ELIZA H. BOOT
Journal: JAMA (1899)

Child-bearing, though a physiologic function, is not without danger to both mother and child. Danger arises from two distinct sources. The first is external to the mother, and depends on her environment, in which her safety is menaced by infections that may occur during gestation, during labor, and during the period of lying in. The second source of danger is internal in nature. It belongs within the woman herself, growing out of conditions that make the passage of the passenger unsafe or impossible. It finds expression in faulty physical development for which our modern methods of living are largely responsible; in faulty development of the parts concerned in parturition, and in accidents of mechanism. The treatment of the first source of danger must be prophylactic and remedial, while that of the second must be mechanical, and includes a wide range of surgery. If a perfect prophylaxis is observed, remedial measures will fall into disuse, while a thorough knowledge of, and training in, methods
Hemopoietic origin of factor XIII A subunits in platelets, monocytes, and plasma. Evidence from bone marrow transplantation studies.
Authors: M C Poon, J A Russell, S Low, G D Sinclair, A R Jones, W Blahey, B A Ruether, D I Hoar
Journal: Journal of Clinical Investigation (1989)

Factor XIII A subunit (FXIIIA) is found in plasma, platelets, and monocytes. The hemopoietic contributions to FXIIIA in these components were studied in patients transplanted with marrows from donors with different FXIIIA phenotypes. In three patients with successful engraftment (by DNA genotyping, red cell phenotyping, and cytogenetic studies) platelet and monocyte FXIIIA changed to donor phenotypes with hematologic recovery. Thus, FXIIIA in platelets and monocytes is synthesized de novo and/or from their progenitor cells. Plasma FXIIIA phenotype change after transplantation was more complex. Patient I changed from phenotype 1-1 (one electrophoretically fast band) to 1-2 (three bands) in 115 d; patients 2 and 3 did not change completely from phenotype 1-2 to 1-1 in up to 458 d, but did show enrichment of the fastest band. Thus, while there is a definite contribution of donor hemopoiesis to plasma FXIIIA, another source of recipient FXIIIA appears to be present to delay or prevent the phenotype change.
PATHOLOGY OF ACQUIRED HEART DISEASE IN CHILDREN.
Authors: J. DUTTON STEELE
Journal: JAMA (1900)

When asked to write upon this subject for the Symposium of the Pediatric Society I realized how hard it is to make such a paper more than a mere catalogue of lesions. To avoid this it has seemed better and more profitable to consider the subject in a comparative light, and to take the pathologic changes in the adult as a standard by which to develop the difference in the pathology of the child heart, together with some inquiry as to the causes of these disturbances. With such an object in view it seems best to take up first the conditions of nutrition and disease particularly liable to affect the heart in childhood. <h3>NUTRITION OF THE HEART IN CHILDHOOD.</h3> It is a general law that the tissues respond more quickly and more readily to stimulation and grow more vigorously in early life than after puberty. A corollary to this is
Chemotherapy Alone for Early Hodgkin's Lymphoma: An Emerging Option
Authors: George P. Canellos
Journal: Journal of Clinical Oncology (2005)

Early stage Hodgkin’s lymphoma is a highly curable disease. Combined chemotherapy and radiation has resulted in high freedom-from-progression rates at 5 to 12 years in the range of 93% for stages I and II patients with asymptomatic presentations and approximately 85% for those with unfavorable disease characteristics. 1-3 The revelation of serious cardiac and second malignancy issues in long-term survivors treated with radiotherapy has prompted a reconsideration of its role when used alone or combined with chemotherapy. Thus, there is a serious need to assess the benefits of chemotherapy alone in patients with early stage disease, especially in those without bulky presentations. In this issue of the Journal of Clinical Oncology is the publication of a trial conducted by the National Cancer Institute of Canada (NCI-C) in collaboration with the Eastern Cooperative Oncology Group (ECOG) addressing the role of chemotherapy alone for early-stage Hodgkin’s lymphoma. 4 The trial was conceived in the early 1990s, when subtotal nodal radiation therapy with splenic irradiation was the standard treatment in Canada for clinically staged patients with early nonbulky stage I to IIA disease. The experimental arm was the chemotherapy regimen of doxorubicin, bleomycin, vincristine and dacarbazine (ABVD) alone for four cycles if a complete response (CR) was achieved after two cycles. Otherwise, patients received six cycles. The standard arm was radiation therapy alone, unless one of the following was present: erythocyte sedimentation rate (ESR) 50 mm/h, or four or more nodal sites, in which case patients received two cycles of ABVD before protocol irradiation. Approximately 70% of 399 total patients had one or two of these unfavorable features. Thus, for a considerable fraction of the patient population, the study was a comparison of combined-modality therapy with chemotherapy alone. At a median follow-up of 4.3 years, freedom from progression (FFP) was the only parameter that reached statistical significance, in which the standard arm had a FFP of 94% compared with 88% for chemotherapy alone (P .04). This difference was confined to the unfavorable group. Further, there were no differences in the event-free and overall survivals. Although the standard arm of this trial is no longer used, subsequent trials have confirmed that combined-modality therapy is superior in FFP compared to radiation alone and that chemotherapy with involved-field radiation therapy is comparable in benefit to more extensive-field radiation plus the same chemotherapy. 5
Assessment of oxygen supplementation during air travel.
Authors: D. Cramer, S. Ward, D. Geddes
Journal: Thorax (1996)

The aim of this study was to simulate an in flight environment at sea level with a fractional inspired concentration of oxygen (FiO2) of 0.15 to determine how much supplemental oxygen was needed to restore a subject's oxygen saturation (SaO2) to 90% or to the level previously attained when breathing room air (FiO2 of 0.21).Three groups were selected with normal, obstructive, and restrictive lung function. Using a sealed body plethysmograph an environment with an FiO2 of 0.15 was created and mass spectrometry was used to monitor the FiO2. Supplemental oxygen was administered to the patient by nasal cannulae. SaO2 was continuously monitored and recorded at an FiO2 of 0.21, 0.15, and 0.15 + supplemental oxygen.When given 2 l/m of supplemental oxygen all patients in the 15% environment returned to a similar SaO2 value as that obtained using the 21% oxygen environment. One patient with airways obstruction needed 3 l/m of supplemental oxygen to raise his SaO2 above 90%.This technique, which simulates an aircraft environment, enables an accurate assessment to be made of supplemental oxygen requirements.
THROMBOSIS OF INTERIOR TEMPORAL BRANCH OF THE RIGHT RETINAL VEIN SUCCESSFULLY TREATED WITH HEPARIN
Authors: R. R. Ferguson
Journal: JAMA (1941)

Among the recently developed clinical applications of heparin therapy is the treatment of thrombosis of the central retinal vein or its tributaries. Although it is likely that work had been done earlier and not reported, prominence was first given to the subject in 1938 when the<i>Lancet</i>published two articles with complete case reports. In the same year a third case was reported by Ploman<sup>1</sup>in<i>Acta ophthalmologica</i>. Holmin and Ploman<sup>2</sup>describe the improvement in thrombosis of the central vein of the retina after treatment with heparin. Following this presentation by a few months was a paper by Boström and William-Olsson<sup>3</sup>in which is recorded the satisfactory clinical course in a similar case under heparin therapy. Prompted by the encouraging results thus reported, I elected to employ heparin in the treatment of a patient with thrombosis of the inferior temporal branch of the right central vein of
Updated Hodgkin's disease. Current status of lymphography
Authors: M. Viamonte
Journal: JAMA (1972)

Characteristic findings in Hodgkin's disease are the lacunar patterns (micro lacunary and macrolacunary defects) that are seen as punched out, rounded, small, or large filling defects in the nodes.<sup>51-53</sup>Minimal distortion of nodal architecture and normal or minimally disturbed contour of the nodes are frequent findings. Pelvic and para-aortic node involvement by Hodgkin's disease may occur histologically, despite the normality of the adenographic pattern by lymphography. In some types of Hodgkin's disease with diffuse fibrosis, the lymph node architecture may not be recognized because of total replacement of the lymph nodes by disease. Nonspecific enlargement of otherwise normallooking lymph nodes, and coarse reticular pattern may be observed occasionally. Increased numbers of nodes are seen often in infants and children. There are no adenographic patterns pathognomonic of Hodgkin's disease.<sup>53</sup>Total replacement of nodal architecture can be seen with diffuse metastatic disease following retroperitoneal adenectomy, and in patients with retroperitoneal
Anencephalic Newborns as Organ Donors: A Critique
Authors: John D. Arras
Journal: JAMA (1988)

THE DEBATE over whether anencephalic newborns should be used as organ donors<sup>1,2</sup>has entered a new phase with the recent announcements from West Germany<sup>3</sup>and California (<i>New York Times</i>, Oct 19, 1987, p Al) of kidney and heart transplants from anencephalic newborns. As we move from deliberation and debate to action, there is an urgent need to reflect on the ethical implications of this controversial procedure. <h3>The Issues</h3> The case for taking hearts, paired kidneys, and other vital organs from anencephalic newborns is based on two distinct needs. First, there are many chronically ill infants, children, and adults who may benefit from organ transplant, and there is a relative scarcity of available donors. Second, there is the need of the parents of an anencephalic infant to salvage some good from a tragic situation. Allowing the infant to be used as an organ donor may help satisfy this need.
Management of Dog Bite Wounds-Reply
Authors: Michael Callaham
Journal: JAMA (1981)

<h3>In Reply.—</h3> Space limitations did not permit a detailed discussion of wound-edge excision in my article on dog bite wounds. This technique consists of the usual debridement of devitalized tissue, followed by carefully trimming off about 5 mm of the wound edge with a scalpel. It does not refer to total excision of the entire wound. Producing a straight and properly squared-off edge requires some practice, but no more so than other common suturing techniques. Most dog bite wounds can be closed easily and rapidly by this method by any physician experienced in suturing. The complications listed by Dr Lehv are all theoretically possible, but only likely in situations where much larger quantities of tissue are removed. Dr Lehv's experience that "most dog bite wounds are reasonably clean, sharp, and linear" is unusual. Virtually all physicians have found otherwise, and they therefore recommend such debridement and limited excision. Cases involving
Effects of neurokinin depletion on airway inflammation induced by chronic antigen exposure.
Authors: I F Tibério, G M Turco, E A Leick-Maldonado, R S Sakae, S O Paiva, M do Patrocínio, T N Warth, J R Lapa e Silva, P H Saldiva, M A Martins
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We assessed the effects of neurokinin (tachykinin) depletion by capsaicin (CAP) treatment on airway inflammation induced by repeated ovalbumin (OA) aerosol exposures (twice a week for 4 wk) in guinea pigs. The animals were then anesthetized, tracheostomized, mechanically ventilated and challenged with ovalbumin aerosol. Maximal values of respiratory system resistance and elastance after antigen challenge were significantly lower in capsaicin-treated guinea pigs than in intact animals (p < 0.001). Morphometric analysis of noncartilaginous airways revealed less intense bronchoconstriction (p < 0.001) and peribronchiolar edema (p < 0.001) in capsaicin-treated guinea pigs. Chronic antigen exposure resulted in a significant increase in lymphocytes and eosinophils both in bronchoalveolar lavage (BAL) fluid and airway wall. Immunohistochemistry with monoclonal antibodies revealed that most of the lymphocytes present in airway wall were CD4+ T cells. Capsaicin treatment resulted in values of CD4+ T cells in airway wall significantly lower than non-capsaicin-treated guinea pigs (p < 0.005). This difference was not observed in eosinophil recruitment. Our results suggest that neurokinin release by sensory nerve terminals results in an amplification of the pulmonary inflammatory changes induced by chronic antigen exposure. In addition, neurokinins play a role in T-cell recruitment induced by chronic allergen exposure.