tbuckley/cabot-search huggingface dataset:
Endogenous Nitric Oxide Masks α <sub>2</sub> -Adrenergic Coronary Vasoconstriction During Exercise in the Ischemic Heart
Authors: Yutaka Ishibashi, Dirk J. Duncker, Robert J. Bache
Journal: Circulation Research (1997)

Previously, we observed that alpha 1-but not alpha 2-adrenergic vasoconstriction restricted blood flow distal to a coronary artery stenosis that resulted in myocardial hypoperfusion during exercise. This study was performed to test the hypothesis that vascular smooth muscle alpha 2-adrenergic vasoconstriction during exercise does exert a flow-limiting effect distal to a coronary artery stenosis but that this action is counterbalanced by simultaneous endothelial alpha 2-adrenergic stimulation of NO production. Eight dogs instrumented with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD) were studied during treadmill exercise in the presence of a coronary artery stenosis before and during infusion of the alpha 2-adrenergic receptor antagonist idazoxan (1.0 microgram.kg-1.min-1 IC) before and after NO synthase blockade with NG-monomethyl-L-arginine (LNNA, 1.5 mg/kg IC). Coronary pressure distal to the stenosis was maintained constant during the control period and after administration of idazoxan before and after LNNA. Neither idazoxan nor LNNA altered any of the systemic hemodynamic variables either at rest or during exercise. During exercise in the absence of a stenosis, idazoxan and LNNA had no effect on coronary blood flow. In the presence of a stenosis that decreased distal coronary pressure to 52 +/- 3 mm Hg, mean myocardial blood flow measured with microspheres was 0.87 +/- 0.17 mL.min-1.g-1 in the LAD-dependent region and 2.52 +/- 0.30 mL.min-1.g-1 in the posterior control region, respectively. With no change in distal coronary pressure, idazoxan had no effect on mean myocardial blood flow in the LAD region (0.86 +/- 0.17 mL.min-1.g-1), but LNNA decreased mean myocardial blood flow to 0.49 +/- 0.09 (P < .01). However, when idazoxan was infused during exercise in the presence of a coronary artery stenosis after LNNA administration, idazoxan increased mean myocardial blood flow to 0.62 +/- 0.13 mL.min-1.g-1 (P < .01). These data demonstrate that alpha 2-adrenergic stimulation of endothelial NO production, which occurs during exercise in the presence of a flow-limiting coronary artery stenosis, acts to counterbalance vascular smooth muscle alpha 2-adrenergic vasoconstriction.
Doesn't it make you sick
Authors: R. Anthony-Pillai
Journal: BMJ (2003)

An elderly Serbian woman recently presented to the hospice with symptoms of persistent nausea. She had developed breast cancer in 1980 and had undergone a mastectomy. Her disease had relapsed in 1993 and 1997. She had a history of hypothyroidism and asthma. She had been taking regular inhalers, thyroxine, and slow release aminophylline for many years.

In December 2002 she was admitted to a London teaching hospital with nausea and vomiting; trialtreatment with cyclizine, levomepromazine, and metoclopramide met with limited success. Her thyroid function tests were normal, as were …
Prevention of Hepatitis in Day-Care Centers-Reply
Authors: Stephen C. Hadler
Journal: JAMA (1983)

<h3>In Reply.—</h3> The points raised by Dr Holmes are well taken. The works of Capps and colleagues in the 1950s not only served as models for recent studies of hepatitis A in day-care centers but helped to inspire initiation of these studies.<sup>1</sup>The lessons in both postexposure treatment and preexposure prevention have not been lost to those persons who deal with this problem. Certainly the cornerstone of disease control in a day-care setting must be educational programs aimed at maximizing hygienic standards in day-care centers. Such programs must be broadly conceived to be applicable not only for hepatitis A but also for the other enteric diseases—shigellosis and rotavirus,<i>Giardia</i>, and<i>Campylobacter</i>infections—that have been recognized as disease threats in day-care centers.<sup>2</sup>Such programs should be primarily for day-care employees and directors who are directly responsible for establishing and implementing appropriate hygienic practices in a day-care setting. But to
Powerful Genes — Myostatin Regulation of Human Muscle Mass
Authors: Elizabeth M. McNally
Journal: New England Journal of Medicine (2004)

In this issue of the Journal, Schuelke et al. (pages 2682–2688) describe a child with substantial muscle hypertrophy and a splice-site mutation in the gene encoding myostatin. Myostatin is a member of the transforming growth factor β (TGF-β) family. Members of this family are diverse but have in common the regulation of growth and differentiation from the earliest stages of embryogenesis to mature adult tissues and cell types. Myostatin, or growth and differentiation factor 8 (GDF-8), was first defined as a negative regulator of muscle mass on the basis of a mouse model from which the gene encoding myostatin had . . .
Acrokeratosis paraneoplastica (Bazex syndrome) associated with primary cutaneous squamous cell carcinoma of the lower leg, vitiligo and alopecia areata
Authors: M. HARA, M. HUNAYAMA, S. AIBA, T. SUETAKE, M. WATANABE, M. TANAKA, H. TAGAMI
Journal: British Journal of Dermatology (2006)

We report a case of acrokeratosis paraneoplastica (AP; Bazex syndrome), characterized by typical palmoplantar hyperkeratosis and psoriasiform scaly erythema of the acral regions, associated with primary cutaneous squamous cell carcinoma (SCC) on the left lower leg. This 54-year-old Japanese man subsequently developed vitiligo, and alopecia areata of the scalp. Serial monitoring of squamous cell carcinoma antigen (SCC-Ag) demonstrated that the severity of the clinical manifestations of AP paralleled the serum concentrations of SCC-Ag. We suggest that an immune-mediated mechanism underlies the development of AP in this patient.
Diagnostic Use of Radioactive Xenon Clearance and a Standardized Walking Test in Obliterative Arterial Disease of the Legs
Authors: J. ALPERT, H. GARCIA DEL RIOÓ, N. A. LASSEN
Journal: Circulation (1966)

The 133 Xe clearance method was used for studying the muscle blood flow (MBF) and the time course of the hyperemic reaction in the calf muscles during walking. Methodological observations showed that the type of walking markedly influenced the hyperemic reaction. However, even during steady-state walking in trained subjects a variability of 15 to 20% in the muscle blood flow was noted in repeated tests. Clinical studies were made in 11 patients with occlusive arterial disease of the femoral artery and intermittent claudication. Twelve control subjects were also studied. On use of a standardized and fairly strenuous walking test on a treadmill, all 18 legs with intermittent claudication showed abnormal 133 Xe clearance curves from the anterior tibial, the soleus, and the gastrocnemius muscles. All the curves disclosed subnormal MBF during walking and prolonged post-exercise hyperemia. It is concluded that this 133 Xe clearance test constitutes a very direct and diagnostically valuable method for disclosing the basic pathophysiological mechanism underlying intermittent claudication.
The Relationship of 1-131 6p-lodomethyl-19- Norcholesterol (NP-59) Adrenal Cortical Uptake to Indices of Androgen Secretion in Women with Hyperandrogenism
Authors: M D GROSS, B SHAPIRO, J E FREITAS, J AYERS, D P SWANSON, M C WOODBURY, D E SCHTEINGART, W H BEIERWALTES
Journal: Clinical Nuclear Medicine (1984)

Dexamethasone suppression (DS) adrenal cortical scintigraphy has been shown to be useful in the detection of the adrenal pathology in women with hyperandrogenism. However, a relationship between adrenal cortical uptake of I-131 6 beta-iodomethylnorcholesterol (NP-59) and the level of adrenal androgen secretion has not been established. A retrospective analysis of DS adrenal scintiscans has been performed on 39 women with hirsutism and hyperandrogenism. In 14 patients with normal patterns of imaging, in vivo adrenal gland iodocholesterol uptake, calculated using a semi-operator-independent-computer algorithm, did not correlate with the excretion of urinary 17-ketosteroids (17-KS). In contrast, in 20 patients demonstrating abnormal bilateral early imaging patterns, adrenal gland NP-59 uptake correlated significantly with the level of urinary 17-KS excretion (r = 0.65, P less than 0.05). To date seven of these 20 patients have had confirmatory procedures documenting the adrenal glands as contributing sites of androgen secretion. A similar correlation with urinary 17-KS excretion was seen in five other patients with unilateral imaging patterns (r = 0.94, P less than 0.005), due to androgen-secreting adrenal cortical adenomas. No correlation between adrenal NP-59 uptake and plasma testosterone or dehydroepiandrosterone sulphate levels was observed in any of the groups. Thus, adrenal gland uptake of NP-59 under DS reflects a measure of androgen secretion in women with androgen excess.
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: A. M. Pappenheimer, Robin Brown
Journal: The Journal of Experimental Medicine (1968)

Using the technique of radioautography, it has been shown that a probable maximum of only 25-50 molecules iodine-125-labeled toxin per cell is bound by human HeLa cells treated with approximately 10(7) molecules of toxin per cell, or just under one saturating dose. Radioautographs of sections from labeled cells locate most if not all of the toxin molecules fixed to the outer cell membrane. Under identical conditions far less label is taken up by mouse L cells. It is probable that the resistance of this species to diphtheria toxin can be accounted for in terms of the failure of mouse cells to bind the toxin protein. The irreversible inhibition of protein synthesis in a living cell culture by a few molecules of toxin located at the cell surface is discussed in relation to the known interaction between toxin, NAD, and transferase II in mammalian cell extracts.
Letter: Glamourizing the consultant.
Authors: J D Ward
Journal: BMJ (1974)

<h3>Abstract</h3> The failure of adult CNS neurons to survive and regenerate their axons after injury or in neurodegenerative disease remains a major target for basic and clinical neuroscience. Recent data demonstrated in the adult mouse that exogenous expression of Sry-related high-mobility-box 11 (Sox11) promotes optic nerve regeneration after optic nerve injury but exacerbates the death of a subset of retinal ganglion cells (RGCs), α-RGCs. During development, Sox11 is required for RGC differentiation from retinal progenitor cells (RPCs), and we found that mutation of a single residue to prevent SUMOylation at lysine 91 (K91) increased Sox11 nuclear localization and RGC differentiation <i>in vitro</i>. Here, we explored whether this Sox11 manipulation similarly has stronger effects on RGC survival and optic nerve regeneration. <i>In vitro</i>, we found that non-SUMOylatable Sox11<sup>K91A</sup> leads to RGC death and suppresses axon outgrowth in primary neurons. We furthermore found that Sox11<sup>K91A</sup> more strongly promotes axon regeneration but also increases RGC death after optic nerve injury <i>in vivo</i> in the adult mouse. RNA sequence (RNA-seq) data showed that Sox11 and Sox11<sup>K91A</sup> increase the expression of key signaling pathway genes associated with axon growth and regeneration but downregulated <i>Spp1</i> and <i>Opn4</i> expression in RGC cultures, consistent with negatively regulating the survival of α-RGCs and ipRGCs. Thus, Sox11 and its SUMOylation site at K91 regulate gene expression, survival and axon growth in RGCs, and may be explored further as potential regenerative therapies for optic neuropathy.
Acute Lymphoblastic Leukemia in a Patient Receiving Penicillamine for Wilson's Disease
Authors: Priscilla Ann Gilman
Journal: JAMA (1982)

Acute lymphoblastic leukemia developed in a girl with Wilson's disease after 37 months of high-dose penicillamine therapy. We postulate that penicillamine-induced alterations in host immunity may cause a predisposition to certain malignancies, similar to that which occurs in other acquired or inherited immunodeficiency states. (<i>JAMA</i>1982;248:467-468)
SS‐B/La antigen purification, and ELISA detection of anti‐SS‐B/La antibodies in sera from patients with inflammatory connective tissue diseases
Authors: B. Hansen, P. Larseb, R. Manthorpe
Journal: Allergy (1988)

SS‐B/La antigen was purified by immunoadsorbent columns with immunoglobulin from a patient with primary Sjögren's syndrome. Monitoring of the purification was facilitated by the fused rocket‐immunoelectrophoresis technique. Technical ELISA variables for the detection of serum antibodies against the SS‐B/La antigen were evaluated, and a recommended procedure is described. Prospective investigation of anti‐SS‐B/La antibodies in 103 blood donors and 131 patients with chronic inflammatory connective tissue diseases, including 43 patients with primary Sjögren's syndrome was performed. Anti‐SS‐B/La antibody concentrations were above normal in 65% of the patients with primary Sjögren's syndrome (verified by the strictly objective Copenhagen criteria for keratoconjunctivitis sicca and xerostomia) and 9% of patients with other chronic connective tissue diseases. The predictive value for primary Sjögren's syndrome among patients with increased levels of the anti‐SS‐B/La antibodies attending a rheumatology clinic was 78%.
Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool
Authors: Fraia Melchionda, Terry J. Fry, Matthew J. Milliron, Melissa A. McKirdy, Yutaka Tagaya, Crystal L. Mackall
Journal: Journal of Clinical Investigation (2005)

Current models of T cell memory implicate a critical role for IL-7 in the effector-to-memory transition, raising the possibility that IL-7 therapy might enhance vaccine responses. IL-7 has not been studied, to our knowledge, before now for adjuvant activity. We administered recombinant human IL-7 (rhIL-7) to mice during immunization against the male antigen HY and compared these results with those obtained from mice immunized with rhIL-2 and rhIL-15. Administration of rhIL-7 or rhIL-15, but not rhIL-2, increased effector cells directed against these dominant antigens and dramatically enhanced CD8(+) effectors to subdominant antigens. The mechanisms by which the cytokines augmented effector pool generation were multifactorial and included rhIL-7-mediated costimulation and rhIL-15-mediated augmentation of the proliferative burst. The contraction phase of the antigen-specific response was exaggerated in cytokine-treated mice; however, CD8(+) memory pools in rhIL-7- or rhIL-15-treated groups demonstrated superior long-term survival resulting in quantitative advantages that remained long after the cytokines were discontinued, as demonstrated by improved survival after challenge with an HY-expressing tumor undertaken several weeks after cytokine cessation. These results confirm the adjuvant activity of rhIL-15 and demonstrate that rhIL-7 also serves as a potent vaccine adjuvant that broadens immunity by augmenting responses to subdominant antigens and improving the survival of the CD8(+) T cell memory pool.
ON THE DIAGNOSIS OF GASTRIC ULCER.
Authors: L. HARRISON METTLER
Journal: JAMA (1896)

A disease that causes no less than 5 per cent. of all deaths and that can only be "approximately" diagnosed in the absence of hematemesis is still deserving of the closest study. The following case is presented as a text for a discussion upon the hitherto known signs of gastric ulcer. N. H., aged 27, first came under my observation Nov. 29, 1893, through the kindness of Drs. Lyman and Ward, after a profuse hematemesis. Neither the family history of the young woman nor that of her early life presented anything of special note. Having somewhat of a neurotic type of constitution, she nevertheless has always borne the appearance of fairly good health, being well nourished and well developed. She has always been of a studious turn of mind and devoted much time to music and literature. She is fond of outdoor sports and is an expert bicyclist. Except for
Psychological Outcome, Fatigue, and Quality of Life After Infection With Shiga Toxin–Producing Escherichia coli O104
Authors: Bernd Löwe, Viola Andresen, Katharina Fraedrich, Kerrin Gappmayer, Karl Wegscheider, András Treszl, Björn Riegel, Matthias Rose, Ansgar W. Lohse, Wiebke Broicher
Journal: Clinical Gastroenterology and Hepatology (2014)
OBSERVATIONS ON SOME CAUSES OF GALL STONE FORMATION
Authors: Peyton Rous, Douglas R. Drury, Philip D. McMaster
Journal: The Journal of Experimental Medicine (1924)

A day-to-day study has been made of the sediment in the sterile liver bile of intubated dogs. There exists a marked tendency for calcium carbonate to be deposited therefrom. After hepatic or duct injury a great deal of organic débris of various sorts may be present in the bile, but it never causes deposition out of the fluid save when it accumulates in quantity on the tube wall. Particles of the material of which "bile thrombi" are composed may be found in the bile when the liver has been appropriately damaged, but these fail to act as centers of stone formation. On the other hand, there are to be found in the secretion after many sorts of hepatic injury little nuclei which undoubtedly serve in this way. These nuclei consist of a mixture of calcium bilirubinate and carbonate with an organic shadow or scaffolding. They do not occur in normal bile, but, coming down on special occasions, prove favorable to deposition out of the secretion elaborated at later periods. We have found nuclei strikingly similar in their relationship to stone formation, but consisting almost wholly of carbonate, in the sterile bile from human gall bladders which contained large calculi. Many of them were encountered in a free state, and others with layers of cholesterol and organic matter upon their surface, while others yet were recognizable deep within matured stones. The factors concerned in the genesis of gall stones consisting of calcium carbonate have been reviewed at some length in this paper and the preceding one. The evidence we have collected supports the view that the development of carbonate stones in human beings as well as in the dog may be a consequence, not of changes in the bile brought about by microorganisms, nor of the elaboration of an inflammatory exduate rich in calcium salts, but merely of inflammation such as leads to lessened motility of the duct system with the accumulation of organic débris. The fact that infection is almost the sole agent whereby such inflammation is set up and maintained in clinical instances had led too often to the conclusion that it serves as the essential agent in the process of calcification. The present findings taken with those described in a preceding paper suffice for an understanding of the immediate history of the gall stones which develop in intubated dogs. But the factor of individual differences, as yet undefined in nature, bulks large in the problem of the lithiasis, as does that of the local physiological safeguards against it.
PHENOLTETRACHLORPHTHALEIN LIVER FUNCTION TEST
Authors: SIEGFRIED MAURER
Journal: JAMA (1925)

Phenoltetrachlorphthalein was studied in 1909 as a subcutaneous purgative.<sup>1</sup>In doses of 5 mg. per kilogram of body weight, it was found to be chiefly excreted in the bile, and partly reabsorbed in the colon. When given intravenously in larger doses, it appears in all the body secretions. The fact that when injected intravenously in doses of 5 mg. per kilogram of body weight it was excreted chiefly in the bile led Rowntree, Hurwitz and Bloomfield<sup>2</sup>to use as an index of liver function the determination of the quantity recoverable in the feces in the first forty-eight hours after injection. This quantitative determination was so laborious and time consuming that it was not practical as a clinical test. This objection was overcome by McNeil,<sup>3</sup>who attempted to determine quantitatively the dye in the duodenal contents, and later modified by Aaron, Beck and Schneider,<sup>4</sup>who determined the
Pharmacodynamic Effects of Beta-Adrenergic Receptor Blockade in Patients with Hyperthyroidism *
Authors: William R. Wilson, Ernest O. Theilen, Fred W. Fletcher
Journal: Journal of Clinical Investigation (1964)

The interrelationships of thyroid hormone, the adrenal medulla, and the sympathetic nervous sys- tem have been recognized since the early part of the present century (1-4).More recent studies of experimental hyperthyroidism by Brewster, Isaacs, Osgood, and King (5) supported the hy- pothesis that the sympathetic nervous system may be responsible for the metabolic and hemodynamic changes associated with the hypermetabolic state, since the alterations induced by thyroid feeding could be reversed by epidural block.Recent trials of reserpine (6, 7) and guanethi- dine (7-9) that release catecholamines and de- plete the tissues of them have shown that these drugs can partially alleviate some clinical manifes- tations of thyrotoxicosis.'The cardiac rate may be slowed, but consistent and significant reductions of the high cardiac output in patients with hyper- thyroidism have not been reported, except by Gold- stein, Furth, Becker, and Killip (10) using gua- nethidine.Methyldopa, a decarboxylase inhibitor, also slows the pulse rate of patients with hyper- thyroidism, but does not significantly change the clinical manifestations (11), or reduce the ele- vated cardiac output or oxygen consumption (12).Furthermore, a continuous infusion of phentola- mine (Regitine) in a hyperthyroid patient does not alter cardiac output (13), since it blocks alpha-rather than beta-adrenergic receptors.If the sympathetic nervous system is a crucial medi- ator of the hemodynamic changes in hyperthyroid- ism, it seems logical to explore the part that beta *
Validation of the modified allergic rhinitis and its impact on asthma (<scp>ARIA</scp>) severity classification in allergic rhinitis children: the <scp>PEDRIAL</scp> study
Authors: J. Montoro, A. Del Cuvillo, J. Mullol, X. Molina, J. Bartra, I. Dávila, M. Ferrer, I. Jáuregui, J. Sastre, A. Valero
Journal: Allergy (2012)

Abstract Background A modified allergic rhinitis and its impact on asthma ( ARIA ) (m‐ ARIA ) criterion to classify the severity of allergic rhinitis ( AR ) has recently been validated in both treated and untreated adult patients; however, such information in children is lacking. The aim of this study was to validate this m‐ ARIA severity criterion, which allows for discrimination between moderate and severe AR , in a large pediatric patient sample population. Methods The m‐ ARIA classification categorizes AR severity into mild (no affected items), moderate (1–3 affected items), and severe (all four affected items). We applied this modified criterion to untreated AR pediatric patients aged 6–12 years, through an observational, cross‐sectional, and multicenter study. AR symptoms were assessed using the Total Four Symptom Score (T4 SS ), and the severity was evaluated by both ARIA severity items and visual analogue scale ( VAS ). Results Allergic rhinitis pediatric patients ( N = 1269) from 271 centers were included. Among them, 59.5% had intermittent and 40.5% persistent disease; 89.9% had moderate/severe AR using the original ARIA (o‐ ARIA ) classification and 59.5% had moderate, while 30.5% had severe AR using the m‐ ARIA criterion. Using the m‐ ARIA , significantly higher T4 SS and VAS scores were obtained when comparing severe with moderate AR . Conclusions The m‐ ARIA severity classification is a useful clinical tool to discriminate moderate from severe AR among untreated pediatric patients.