tbuckley/cabot-search huggingface dataset:
Hodgkin's disease. An immunodepleting and immunosuppressive disorder.
Authors: J J Twomey, A H Laughter, S Farrow, C C Douglass
Journal: Journal of Clinical Investigation (1975)

Irradiated leukocytes or mononuclear leukocytes, from 16 out of 30 patients with Hodgkin's disease and from one patient with the Sézary syndrome, stimulated in culture subnormal (3H)thymidine incorporation by allogeneic lymphocytes from normal individuals. This abnormality was not demonstrated in any of 30 other patients with non-Hodgkin's lymphomas. Subnormal mixed leukocyte culture reaction activation was caused by suppression of the mixed leukocyte reaction by patients' cells. Inhibition of the reaction by patient mononuclear leukocytes was corrected when adherent cells were removed or when protein synthesis was inhibited with cycloheximide. The inhibitory cells were probably lymphocytes since selective removal of phagocytic cells did not remove the inhibition by other patient mononuclear leukocytes. The presence in culture of as few as 2,500 granulocytes per mm3 also reduced responses when target cells were from patients with Hodgkin's disease. Patient cells no longer suppressed the mixed leukocyte reaction after patients entered clinical remission which suggests that suppression is a reversible, disease-related abnormality. Thus, the immune deficiency with advance Hodgkin's disease caused by ly lymphocyte depletion may be compounded by a relative excess of suppressor lymphocytes. The overall immunodeficiency may be further compounded by suppression of immune response by granulocytes at even physiologic concentrations.
The Significance of Dr Fantus' Report
Authors: Byron A. Myhre
Journal: JAMA (1984)

<h3>History of Previous Transfusion Therapy</h3> With the usual availability of adequate amounts and types of blood that we encounter today, it is hard to visualize the difficulty that faced physicians wishing to transfuse before World War II. The account by Louis Diamond<sup>1</sup>chronicles how between the years of 1667 and 1937, the major accent in transfusion therapy was direct transfusion from donor to recipient, usually using some type of arteriovenous anastomosis,<sup>2,3</sup>a pump for direct transfusion,<sup>4</sup>multiple syringes,<sup>5</sup>various stopcocksyringe devices,<sup>6</sup>or, occasionally, a paraffin-lined flask<sup>7</sup>to hold the blood temporarily. No anticoagulant was used, the blood was not stored, all transfusions required the immediate availability of the donor, and the donor had to be bled in the proximity of the patient (often in an operating room). For these reasons, almost all transfusions were elective and given for chronic loss or decreased production of
Observations on Two Cases of Raynaud's Disease (Symmetrical Gangrene). With Chromolithograph
Authors: J. O. Affleck
Journal: BMJ (1888)

complete the operation if the ovaries are not disturbed.If healthy, I think they had better be left alone, and so may the Fallopian tubes.But if the disease has extended higlh up the uterine cavity it would be safer to remove the tubes; and this would add very little to the duration of the operation.I shall not attempt to give the results of this operation statis- tically, but it is important that we should know what a few of the most experienced operators have been able to accomplish.Leopold wrote to me on the 11th of this month, stating that up to that date he had performed total extirpation of the uterus by the vagina in 83 cases with only 5 deaths, a mortality of 6 per cent.PWan, writing on the 13th, says that from 1882 to the end of 1887 he had done 22 operations, 15 successful, but with 7 deaths; but that this year he has had 16 cases, all successful and no deaths.Professor Olshausen, of Berlin, appears to have the largest experience of this operation, for he writes to me that between May, 1887, and November 5th, 1888, he had 99 cases with 13 deaths.In 1881-82, he had 22 cases with 8 deaths; from January, 1883, to April, 1887, 31 cases with 5 deaths = 53 cases in Halle with 13 deaths, to be compared with 99 in Berlin, also 13 deaths.All these were cases of total extirpation by the vagina
Effects of depletion of cells bearing the interleukin-2 receptor on immunoglobulin production and allergic airway responses in the rat.
Authors: P M Renzi, J P Yang, T Diamantstein, J G Martin
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Lymphocytes, key cells in chronic inflammation, are increased in the airways of asthmatics and have increased expression of the interleukin-2 (IL-2) receptor, a sign of activation. We determined the effects of depleting cells bearing IL-2 receptors on immunoglobulin (Ig) production, airway inflammation, and airway responses after antigen challenge of Brown Norway rats that were sensitized to ovalbumin (OA). Both control and ART-18 (antirat IL-2 receptor) antibodies inhibited plasma specific IgE and the early (ER) and late (LR) airway responses to antigen when given from zero to 14 d after sensitization. When ART-18 was administered from 4 to 14 d after sensitization and compared with control animals, it inhibited OA specific IgE production from Day 21 onward, but it increased total IgE and specific IgG. These changes followed a significant increase in blood CD4+ lymphocytes (%) in ART-18-treated animals 14 d after sensitization. The same protocol of administration did not affect Ig levels at 14 d, but it decreased neutrophil influx into the lungs 8 h after antigen challenge without any effects on the ER and LR. Administration of ART-18 at the time of antigen challenge did not affect the subsequent airway inflammation or the increased responsiveness to methacholine that occurs 32 h after antigen challenge. In summary, depletion of IL-2-receptor-bearing cells affects lymphocyte subsets and immunoglobulin production and it decreases the influx of neutrophils into the lungs 8 h after OA challenge, but it does not significantly inhibit the ER, LR, or increased airway responsiveness after antigen challenge.
Thymic stromal lymphopoietin plays divergent roles in murine models of atopic and nonatopic airway inflammation
Authors: K. Yadava, J. Massacand, I. Mosconi, L. P. Nicod, N. L. Harris, B. J. Marsland
Journal: Allergy (2014)

Thymic stromal lymphopoietin (TSLP) is a cytokine primarily produced by epithelial cells, which has been shown to be a potent inducer of T-helper 2 (Th2)-type responses. However, TSLP has pleiotropic effects upon immune cells, and although extensively studied in the context of atopic asthma, its relevance as a therapeutic target and its role in the pathogenesis of nonatopic asthma remains unknown. We sought to investigate the role of TSLP in atopic, nonatopic and viral-induced exacerbations of pulmonary inflammation.Using stringently defined murine models of atopic, nonatopic and virally exacerbated forms of pulmonary inflammation, we compared inflammatory responses of C57BL/6 wild-type (WT) and TSLP receptor-deficient (TSLPR KO) mice.Thymic stromal lymphopoietin receptor (TSLPR) signaling was crucial for the development of atopic asthma. Specifically, TSLPR signaling to lung recruited CD4+ T cells enhanced eosinophilia, goblet cell hyperplasia, and overall inflammation within the airways. In contrast, the absence of TSLPR signaling was associated with strikingly exaggerated pulmonary neutrophilic inflammation in a nonatopic model of airway inflammation. The inflammation was associated with excessive levels of interleukin (IL)-17A in the lungs, indicating that TSLP negatively regulates IL-17A. In addition, in a model of influenza-induced exacerbation of atopic airway inflammation, the absence of TSLPR signaling also led to exaggerated neutrophilic inflammation.Thymic stromal lymphopoietin plays divergent roles in the pathogenesis of atopic and nonatopic asthma phenotypes by either enhancing Th2 responses or curtailing T-helper 17 responses. These findings raise important caveats for the design of therapeutic interventions targeting TSLP in asthma.
Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice.
Authors: H J Peter, H Gerber, H Studer, D V Becker, M E Peterson
Journal: Journal of Clinical Investigation (1987)

Hyperthyroidism caused by nodular goiters is a common disease of aging cats. Growth and iodine metabolism were studied by autoradiography in normal and hyperfunctioning thyroid tissue obtained from cats injected with 125I before surgery, and in xenografts, grown in nude mice, after double-labeling with 131I and [3H]thymidine. Hyperthyroid cat goiters contain single or multiple hyperplastic nodules, consisting of highly cellular tissue with an iodine metabolism exceeding that of the surrounding normal tissue. Xenografts of hyperplastic hot tissue in thyroxine-treated nude mice retain their original histologic pattern and continue to accumulate radioiodine intensely. Autoradiographs assessed for [3H]thymidine incorporation reveal autonomously proliferating follicular cells within the hyperplastic foci but not within the normal tissue. Administration of sera from donor cats into host mice fails to stimulate the xenografts. Neither hyperfunction nor growth of toxic cat goiters depends on extrathyroidal stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells.
Imatinib in Pulmonary Arterial Hypertension Patients with Inadequate Response to Established Therapy
Authors: Hossein A. Ghofrani, Nicholas W. Morrell, Marius M. Hoeper, Horst Olschewski, Andrew J. Peacock, Robyn J. Barst, Shelley Shapiro, Heiko Golpon, Mark Toshner, Friedrich Grimminger, Steve Pascoe
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Pulmonary arterial hypertension (PAH) is a progressive condition with a poor prognosis. Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in its pathobiology.Objectives: To assess safety, tolerability, and efficacy of the PDGFR inhibitor imatinib in patients with PAH.Methods: Patients with PAH in functional classes II–IV were enrolled in a 24-week randomized, double-blind, placebo-controlled pilot study. Patients received imatinib (an inhibitor of PDGFR activity) 200 mg orally once daily (or placebo), which was increased to 400 mg if the initial dose was well tolerated. The primary endpoints were safety and change from baseline in the 6-minute-walk distance (6MWD). Secondary endpoints included hemodynamics and functional classification.Measurements and Main Results: Fifty-nine patients enrolled (imatinib [n = 28]; placebo [n = 31]); 42 completed the study. Dropouts were equally matched between the two groups. In the intention-to-treat (ITT) population there was no significant change in the 6MWD (mean ± SD) in the imatinib versus placebo group (+22 ± 63 versus −1.0 ± 53 m). There was a significant decrease in pulmonary vascular resistance (imatinib −300 ± 347 versus placebo –78 ± 269 dynes · s · cm−5, P < 0.01) and increase in cardiac output (imatinib +0.6 ± 1.2 versus placebo −0.1 ± 0.9 L/min, P = 0.02). Serious adverse events occurred in 11 imatinib recipients (39%) and 7 placebo recipients (23%). Three deaths occurred in each group. Post hoc subgroup analyses suggest that patients with greater hemodynamic impairment may respond better than patients with less impairment.Conclusions: These data from a Phase II study are consistent with imatinib being well tolerated in patients with PAH, and provide proof of concept for further studies evaluating its safety, tolerability, and efficacy in PAH.Clinical trial registered with www.clinicaltrials.gov (NCT00477269).
Hematopoietic origin of hepatic stellate cells in the adult liver
Authors: Eri Miyata, Masahiro Masuya, Shuro Yoshida, Shiho Nakamura, Keizo Kato, Yuka Sugimoto, Tetsunori Shibasaki, Kentaro Yamamura, Kohshi Ohishi, Kazuhiro Nishii, Fumihiko Ishikawa, Hiroshi Shiku, Naoyuki Katayama
Journal: Blood (2007)
Biliary Lipid Secretion in Health and in Cholesterol Gallstone Disease
Authors: Martin C. Carey, Norman A. Mazer
Journal: Hepatology (1984)

The secretory compartment for biliary lecithin and cholesterol secretion probably resides in the smooth endoplasmic reticulum of the hepatocyte. The secretory compartment for bile salts lies predominantly in the enterohepatic circulation which fluxes bile salts continuously through the smooth endoplasmic reticulum compartment and extracts lipids for secretion into bile. Most of bile lecithin is newly synthesized by the liver; most of bile cholesterol is derived from extrahepatic sources. Both cholesterol and lecithin secretion are coupled to bile salt secretion and describe output curves which can be fitted by rectangular hyperbolae: since bile salt secretion is a linear function of input, the relative proportions of cholesterol to bile salts plus lecithin in bile increase at low bile salt outputs. In health, an adequate bile salt (+ lecithin) secretion coupled with normal cholesterol secretion maintains the relative composition of bile in a stable state: fasting compositions usually lie within the micellar zone or metastable supersaturated zone of a triangular coordinate-phase diagram plot. In cholesterol gallstone disease, mean bile salt (+ lecithin) secretion rates are subnormal and/or mean cholesterol secretion rates are supranormal, especially in the fasting state. If individuals are obese there is also enhanced hypersecretion of biliary cholesterol. Either or both secretory defects lead to an elevation and persistence of cholesterol supersaturation of bile. The physical state of the secreted lipids in bile is complex and fluctuant, and probably involves vesicle structures and mixed micelles at high water and cholesterol concentrations and predominantly micellar structures at low water and cholesterol concentrations. In lithogenic bile, the physical state, proportions and nucleation potential of the lipid aggregates are probably different. Further, the respective proportions of biliary mixed micelles and vesicles are probably influenced by the mean hydrophilicity of the bile salt pool.
Incidence Estimate of Nonmelanoma Skin Cancer (Keratinocyte Carcinomas) in the US Population, 2012
Authors: Howard W. Rogers, Martin A. Weinstock, Steven R. Feldman, Brett M. Coldiron
Journal: JAMA Dermatology (2015)

Understanding skin cancer incidence is critical for planning prevention and treatment strategies and allocating medical resources. However, owing to lack of national reporting and previously nonspecific diagnosis classification, accurate measurement of the US incidence of nonmelanoma skin cancer (NMSC) has been difficult. To estimate the incidence of NMSC (keratinocyte carcinomas) in the US population in 2012 and the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in the 2012 Medicare fee-for-service population. This study analyzes US government administrative data including the Centers for Medicare & Medicaid Services Physicians Claims databases to calculate totals of skin cancer procedures performed for Medicare beneficiaries from 2006 through 2012 and related parameters. The population-based National Ambulatory Medical Care Survey database was used to estimate NMSC-related office visits for 2012. We combined these analyses to estimate totals of new skin cancer diagnoses and affected individuals in the overall US population. Incidence of NMSC in the US population in 2012 and BCC and SCC in the 2012 Medicare fee-for-service population. The total number of procedures for skin cancer in the Medicare fee-for-service population increased by 13% from 2,048,517 in 2006 to 2,321,058 in 2012. The age-adjusted skin cancer procedure rate per 100,000 beneficiaries increased from 6075 in 2006 to 7320 in 2012. The number of procedures in Medicare beneficiaries specific for NMSC increased by 14% from 1,918,340 in 2006 to 2,191,100 in 2012. The number of persons with at least 1 procedure for NMSC increased by 14% (from 1,177,618 to 1,336,800) from 2006 through 2012. In the 2012 Medicare fee-for-service population, the age-adjusted procedure rate for BCC and SCC were 3280 and 3278 per 100,000 beneficiaries, respectively. The ratio of BCC to SCC treated in Medicare beneficiaries was 1.0. We estimate the total number of NMSCs in the US population in 2012 at 5,434,193 and the total number of persons in the United States treated for NMSC at 3,315,554. This study is a thorough nationwide estimate of the incidence of NMSC and provides evidence of continued increases in numbers of skin cancer diagnoses and affected patients in the United States. This study also demonstrates equal incidence rates for BCC and SCC in the Medicare population.
THE NATURE, DIAGNOSIS, PROGNOSIS AND TREATMENT OF GENERAL PARESIS
Authors: CHARLES R. BALL
Journal: JAMA (1913)

The honor of having first discovered a relationship between paresis and syphilis belongs to Esmarch and Jessen. These observers in 1857 reported three cases of paresis, the cause of which they attributed to syphilis. Thus a controversy of this subject began which has lasted for more than half a century. The consensus of medical opinion has held that in the great majority of cases syphilis is the chief etiologic factor which causes paresis. Of the opponents of this doctrine Näcke was the most extreme. He considered a neuropathic inheritance as a most important cause and assigned to syphilis an equal importance among other etiologic factors, maintaining that it often furnished the last offense for the development of the disease. It was not until the discovery of the Wassermann reaction and its regular observance in both the blood and spinal fluid of paretics that the doctrine of no syphilis, no paresis,
352 INTERFERON-γ INDUCIBLE PROTEIN-10 (IP-10) IS A PREDICTOR OF OUTCOME DURING THE ACUTE PHASE OF HCV INFECTION
Authors: S. Chokshi, A. Guobuzaite, A. Riva, A. Evans, S. Phillips, A. Ambrozaitis, N. Naoumov
Journal: Journal of Hepatology (2009)
Eosinophilic esophagitis in adults – no clinical relevance of wheat and rye sensitizations
Authors: D. Simon, A. Straumann, A. Wenk, H. Spichtin, H.‐U. Simon, L. R. Braathen
Journal: Allergy (2006)

Background: Eosinophilic esophagitis (EE) is often associated with concomitant atopic diseases. In children with EE in whom food allergens have been identified as causative factors, elemental and elimination diets result in an improvement or resolution of symptoms. Most adult EE patients are sensitized to aeroallergens, which cross‐react with plant‐derived food allergens, most commonly to grass pollen and cereals. Aims of the study: To investigate the clinical relevance of the sensitization to wheat and rye, and the efficacy of an allergen‐specific elimination diet in adult EE patients. Methods: Six patients (five men, one women) with permanently active EE sensitized to grass pollen and the cereals wheat and rye underwent a double‐blind placebo‐controlled food challenge and were kept on an elimination diet avoiding wheat and rye for 6 weeks. Results: The challenge tests with wheat and rye did not provoke any EE symptoms in all patients. The elimination diet failed in reducing disease activity. Although one patient noticed an improvement of symptoms, endoscopic and histopathologic findings remained unchanged. Conclusions: In adult EE patients, sensitization to wheat and rye does not seem causative for EE. Elimination diet is not a reliable and efficient therapeutic measure in EE patients sensitized to wheat and rye. Low specific immunoglobulin‐E levels to wheat and rye may be a consequence of the underlying grass pollen allergy.
Fulminating chromobacterial septicaemia presenting as respiratory distress syndrome.
Authors: T S Lee, B D Wright
Journal: Thorax (1981)

Respiratory distress syndrome occurs in a variety of clinical situations of which sepsis is one important precipitating factor.We have observed and successfully treated with high PEEP (positive end-expiratory pressure) a rare case of chromobacterial septicaemia complicated by an acute respiratory distress syndrome.We describe here the first reported case of a patient in this country surviving this illness with pulmonary involvement. Case reportA 3-year-old white male had been healthy until six days before admission when he developed lethargy, high fever, and bug-bite-like nodular skin lesions on his left hip.This occurred while he and his family were on holiday in Florida.He was admitted to a local hospital and found to have leucocytosis (24-8 x 109/1) with a left shift.The discharge from the skin eruptions was cultured and revealed gram-negative rods which were identified as chromobacteria.He was given gentamicin (7 mg/kg/day) and ampicillin (100 mg/kg/day),which was soon replaced by carbenicillin (600 mg/kg/day) when the chromo- bacteria proved to be ampicillin-resistant.The patient remained febrile, pustules and ulcerative lesions appeared on his extremities, his right index finger became swollen and gangrenous, and he developed grey, watery diarrhoea.The patient was then transferred to the University of Kentucky Medical Center at his parent's request.On arrival, his body temperature was 41 CC, pulse 140/ minute, respiration 25/minute, and blood pressure 120/70 mm Hg.His chest was clear and chest radiographs were normal.A grade II/VI systolic ejection murmer was audible at the apex and left sternal border.White blood count was 22-1 x 109/l and haematocrit 40%.Pro-
Parasite-stress promotes in-group assortative sociality: The cases of strong family ties and heightened religiosity
Authors: Corey L. Fincher, Randy Thornhill
Journal: Behavioral and Brain Sciences (2012)

Throughout the world people differ in the magnitude with which they value strong family ties or heightened religiosity. We propose that this cross-cultural variation is a result of a contingent psychological adaptation that facilitates in-group assortative sociality in the face of high levels of parasite-stress while devaluing in-group assortative sociality in areas with low levels of parasite-stress. This is because in-group assortative sociality is more important for the avoidance of infection from novel parasites and for the management of infection in regions with high levels of parasite-stress compared with regions of low infectious disease stress. We examined this hypothesis by testing the predictions that there would be a positive association between parasite-stress and strength of family ties or religiosity. We conducted this study by comparing among nations and among states in the United States of America. We found for both the international and the interstate analyses that in-group assortative sociality was positively associated with parasite-stress. This was true when controlling for potentially confounding factors such as human freedom and economic development. The findings support the parasite-stress theory of sociality, that is, the proposal that parasite-stress is central to the evolution of social life in humans and other animals.