tbuckley/cabot-search huggingface dataset:
Deoxymyoglobin Is a Nitrite Reductase That Generates Nitric Oxide and Regulates Mitochondrial Respiration
Authors: Sruti Shiva, Zhi Huang, Rozalina Grubina, Junhui Sun, Lorna A. Ringwood, Peter H. MacArthur, Xiuli Xu, Elizabeth Murphy, Victor M. Darley-Usmar, Mark T. Gladwin
Journal: Circulation Research (2007)

Previous studies have revealed a novel interaction between deoxyhemoglobin and nitrite to generate nitric oxide (NO) in blood. It has been proposed that nitrite acts as an endocrine reservoir of NO and contributes to hypoxic vasodilation and signaling. Here, we characterize the nitrite reductase activity of deoxymyoglobin, which reduces nitrite approximately 36 times faster than deoxyhemoglobin because of its lower heme redox potential. We hypothesize that physiologically this reaction releases NO in proximity to mitochondria and regulates respiration through cytochrome c oxidase. Spectrophotometric and chemiluminescent measurements show that the deoxymyoglobin-nitrite reaction produces NO in a second order reaction that is dependent on deoxymyoglobin, nitrite and proton concentration, with a bimolecular rate constant of 12.4 mol/L −1 s −1 (pH 7.4, 37°C). Because the IC 50 for NO-dependent inhibition of mitochondrial respiration is approximately 100 nmol/L at physiological oxygen tensions (5 to 10 μmol/L); we tested whether the myoglobin-dependent reduction of nitrite could inhibit respiration. Indeed, the addition of deoxymyoglobin and nitrite to isolated rat heart and liver mitochondria resulted in the inhibition of respiration, while myoglobin or nitrite alone had no effect. The addition of nitrite to rat heart homogenate containing both myoglobin and mitochondria resulted in NO generation and inhibition of respiration; these effects were blocked by myoglobin oxidation with ferricyanide but not by the xanthine oxidoreductase inhibitor allopurinol. These data expand on the paradigm that heme-globins conserve and generate NO via nitrite reduction along physiological oxygen gradients, and further demonstrate that NO generation from nitrite reduction can escape heme autocapture to regulate NO-dependent signaling.
A disease risk index for patients undergoing allogeneic stem cell transplantation
Authors: Philippe Armand, Christopher J. Gibson, Corey Cutler, Vincent T. Ho, John Koreth, Edwin P. Alyea, Jerome Ritz, Mohamed L. Sorror, Stephanie J. Lee, H. Joachim Deeg, Barry E. Storer, Frederick R. Appelbaum, Joseph H. Antin, Robert J. Soiffer, Haesook T. Kim
Journal: Blood (2012)
Self-renewal potential of NPCs decreased in vitro during human embryonic brain development with reduced activation of mitogen-activated protein kinases signaling
Authors: Lingyu Zhao, Qian Jiao, Xinlin Chen, Pengbo Yang, Bingqiao Zhao, Ping Zheng, Yong Liu
Journal: Molecular Neurodegeneration (2012)

Background Neural progenitor cells (NPCs) are multipotent and selfrenewing cells during development and throughout adulthood. A key question in NPCs transplantation therapies is which stage NPCs from human embryonic brain development are ideal donor. Methods In this study, we investigated the difference of survival, proliferation and apopto sis of NPCs from 12 w, 16 w and 20 w human embryonic brain, and the phosphorylation of mitogen-activated protein kinases (MAPKs) signaling molecules. The NPCs survival was evaluated by trypan blue staining. The NPCs proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, diameter measurement of neurospheres and cell cycle analysis. The cell death of NSCs was evaluated by Hoechst staining. The expression of phosphorylated extracellular signal regulated kinase (ERK), c-Jun N-terminal protein kinase (JNK) and p38 were analyzed by immunoblotting assay. Results The results showed that the survival of human NPCs gradually decreased with human embryonic brain development in vitro; the NPCs proliferation gradually decreased in cell activity, diameter of neurospheres and cell division with human embryonic brain development, and the NPCs apoptosis gradually increased. Phosphorylation of ERK1/2 gradually decreased with human embryonic brain development, however phosphorylation of p38 MAPK gradually increased, and there were no significant change in p-JNK2 level. Conclusions
ACTION OF X-RAYS ON MAMMALIAN CELLS
Authors: Theodore T. Puck, Dimitry Morkovin, Philip I. Marcus, Steven J. Cieciura
Journal: The Journal of Experimental Medicine (1957)

Survival curves of normal human cells from a variety of tissues exposed to varying doses of x-irradiation have been constructed, which permit definition of the intrinsic radiation sensitivity of the reproductive power of each cell type. The mean lethal dose of x-irradiation for all the cells employed, including those from normal and cancerous organs, those exhibiting diploid and polyploid chromosome number; those from embryonic and adult tissues, including recently isolated cells and cultures which had been maintained in vitro for many years, and cells exhibiting either epithelioid or fibroblastic morphology, was found to be contained between the limits of 50 to 150 r. Other similarities in the pattern of radiation effects, such as giant formation and abortive colonial growth, in these cells and that of the HeLa S3, previously studied, confirm the hypothesis that the pattern of reaction to x-irradiation previously elucidated, is representatative, at least in over-all outline, for a large variety of human cells. While the radiation survival curves of various human cells are similar in the gross, small but important characterizing differences have been found. All epithelioid cells so far studied are approximately 2-hit, and more radioresistant than the fibroblast-like cells whose survival data correspond to a mean lethal dose of around 60 r, and which so far can be fitted by either 1-hit or 2-hit curves. The earlier prediction that the major radiobiologic damage to mammalian cells is lodged in the genetic apparatus was confirmed by the demonstration of high frequency of mutants among the survivors of doses of 500 to 900 r. All the data on the x-radiosensitivity of these cells can be explained on the basis of a defect resulting from primary damage localized in one or more chromosomes. These considerations afford a convincing explanation of several aspects of the mammalian radiation syndrome.
A biologically based model of growth and senescence of Syrian hamster embryo (SHE) cells after exposure to arsenic.
Authors: K H Liao, D L Gustafson, M H Fox, L S Chubb, K F Reardon, R S Yang
Journal: Environmental Health Perspectives (2001)

We modified the two-stage Moolgavkar-Venzon-Knudson (MVK) model for use with Syrian hamster embryo (SHE) cell neoplastic progression. Five phenotypic stages are proposed in this model: Normal cells can either become senescent or mutate into immortal cells followed by anchorage-independent growth and tumorigenic stages. The growth of normal SHE cells was controlled by their division, death, and senescence rates, and all senescent cells were converted from normal cells. In this report, we tested the modeling of cell kinetics of the first two phenotypic stages against experimental data evaluating the effects of arsenic on SHE cells. We assessed cell division and death rates using flow cytometry and correlated cell division rates to the degree of confluence of cell cultures. The mean cell death rate was approximately equal to 1% of the average division rate. Arsenic did not induce immortalization or further mutations of SHE cells at concentrations of 2 microM and below, and chromium (3.6 microM) and lead (100 microM) had similar negative results. However, the growth of SHE cells was inhibited by 5.4 microM arsenic after a 2-day exposure, with cells becoming senescent after only 16 population doublings. In contrast, normal cells and cells exposed to lower arsenic concentrations grew normally for at least 30 population doublings. The biologically based model successfully predicted the growth of normal and arsenic-treated cells, as well as the senescence rates. Mechanisms responsible for inducing cellular senescence in SHE cells exposed to arsenic may help explain the apparent inability of arsenic to induce neoplasia in experimental animals.
Maternal Diethylstilbestrol a Time Bomb for Child?
Authors: Kathryn S. Huss
Journal: JAMA (1971)

Clear-cell carcinomas or adenocarcinomas of the vagina, which are appearing in teen-agers and young adults whose mothers received diethylstilbestrol or other synthetic estrogens during pregnancy, recently have assumed great scientific importance. During the late 1940s and early 1950s, estrogen therapy was believed indicated for maintaining pregnancies considered to be at high risk because of bleeding or previous pregnancy loss. Adenocarcinoma of the vagina previously was considered a rare tumor, especially in young women (<i>Cancer</i><b>25</b>:745-757, 1970). Between the years 1966 and 1969, this tumor was diagnosed in eight patients ranging from 15 to 22 years of age, who were treated in two Boston hospitals (seven in one hospital). Medical advice was sought by these adolescent girls and young women because of abnormal bleeding, and hormonal therapy was administered in most cases since the irregular bleeding was assumed to be due to anovulation. Vaginal smears were made in six cases,
Ambient Air Pollution and Apnea and Bradycardia in High-Risk Infants on Home Monitors
Authors: Jennifer L. Peel, Mitchel Klein, W. Dana Flanders, James A. Mulholland, Gary Freed, Paige E. Tolbert
Journal: Environmental Health Perspectives (2011)

Background: Evidence suggests that increased ambient air pollution concentrations are associated with health effects, although relatively few studies have specifically examined infants.Objective: We examined associations of daily ambient air pollution concentrations with central apnea (prolonged pauses in breathing) and bradycardia (low heart rate) events among infants prescribed home cardiorespiratory monitors.Methods: The home monitors record the electrocardiogram, heart rate, and respiratory effort for detected apnea and bradycardia events in high-risk infants [primarily premature and low birth weight (LBW) infants]. From August 1998 through December 2002, 4,277 infants had 8,960 apnea event-days and 29,450 bradycardia event-days in > 179,000 days of follow-up. We assessed the occurrence of apnea and bradycardia events in relation to speciated particulate matter and gaseous air pollution levels using a 2-day average of air pollution (same day and previous day), adjusting for temporal trends, temperature, and infant age.Results: We observed associations between bradycardia and 8-hr maximum ozone [odds ratio (OR) = 1.049 per 25-ppb increase; 95% confidence interval (CI), 1.021–1.078] and 1-hr maximum nitrogen dioxide (OR =1.025 per 20-ppb increase; 95% CI, 1.000–1.050). The association with ozone was robust to different methods of control for time trend and specified correlation structure. In secondary analyses, associations of apnea and bradycardia with pollution were generally stronger in infants who were full term and of normal birth weight than in infants who were both premature and LBW.Conclusions: These results suggest that higher air pollution concentrations may increase the occurrence of apnea and bradycardia in high-risk infants.
Nicotinic Acid in NIDDM-Reply
Authors: Abhimanyu Garg
Journal: JAMA (1990)

In Reply.—  Drs Henkin and Segrest suggest that 4.5 g/d of nicotinic acid is a  dose, which can be questioned. For example, even higher daily doses of nicotinic acid were used by other researchers such as Blankenhorn et al 1 (3 to 12 g), Kane et al 2 (6 to 7.5 g), and Illingworth et al 3 (3 to 8 g). The Coronary Drug Project Research Group 4 used 3 g/d. There is no reason to believe that 3 g/d of nicotinic acid would have markedly different side effects than a dose of 4.5 g/d. Arbitrarily, a daily dose of 1 to 1.5 g of nicotinic acid can be classified as a low dose, 3 to 4.5 g as an intermediate dose, and 6 to 12 g as a high dose. This classification of doses is in line with that suggested by the National Cholesterol Education Program. 5 Our
ESTIMATION OF URINARY SODIUM
Authors: J. Marion Bryant
Journal: JAMA (1949)

<h3>To the Editor:—</h3> My attention has been called to a letter inThe Journalof August 6, page 1172, criticizing the article "Estimation of Urinary Sodium: A Simple Test For Patients on Low Sodium Diets" (J. A. M. A.<b>140</b>:670 [June 25] 1949). The letter states, "Certain misconceptions and questionable features should be discussed publicly, lest they aid in perpetuating ideas and practices now considered out of date." The features pointed out by the correspondent are obvious but are inappropriate to the particular article. The test for the estimation of urinary sodium was proposed for two reasons: (1) because of its simplicity and (2) because clinical trial in our opinion has proved its value. That it is for use by the patient and is only a rough approximation of the urinary sodium with a "large error" was reiterated in the article several times. Furthermore, there is no implication in
CHOLECYSTOGRAPHY IN INFANTS
Authors: Ruth C. Harris
Journal: JAMA (1953)

Roentgen visualization of the gallbladders of infants has been consistently unsatisfactory and has been of little value in diagnosis of lesions of the biliary tract. Satisfactory cholecystograms have been commonly obtained in patients older than three years when the adult dose of either tetraiodophenolphthalein or iodoalphionic acid (Priodax) has been used.<sup>1</sup>As a rule, films have been taken about 14 hours after the oral administration of contrast material. In 1945 Hrdlicka, Watkins, and Robb<sup>2</sup>reported that they had obtained satisfactory gallbladder shadows in two infants 9 and 10 months of age and in three of four infants 12 to 18 months of age. Iodoalphionic acid was used in doses two or three times the usual adult requirement per kilogram of body weight. In infants from one to seven months, no satisfactory gallbladder shadows appeared. Films were made 12 to 18 hours after the oral administration of the contrast
Evidence for Delayed Development of the Glucagon Receptor of Adenylate Cyclase in the Fetal and Neonatal Rat Heart
Authors: Charles M. Clark, Bruce Beatty, Donald O. Allen
Journal: Journal of Clinical Investigation (1973)

The effects, in vivo, of epinephrine, glucagon, and dibutyryl cyclic adenosine 3′,5′-monophosphate (cyclic AMP) on the glycogen content of rat heart and liver and, in vitro, upon adenylate cyclase activity in homogenates of rat heart and liver were determined during the latter third of gestation and the neonatal period. Hepatic glycogen was depleted by epinephrine, glucagon, and dibutyryl cyclic adenosine 3′,5′-monophosphate, but myocardial glycogen was depleted only by epinephrine and dibutyryl cyclic AMP in the neonates. Hepatic adenylate cyclase activity was augmented by both epinephrine (10-5 M) and glucagon (10-5 M), and myocardial cyclase was increased only by epinephrine in tissue obtained from 16, 18, and 20 day fetal rats. Myocardial adenylate cyclase responsiveness to glucagon was present in tissue obtained from rats 4 wk of age and older. It is concluded that in contrast to hepatic adenylate cyclase, myocardial adenylate cyclase in the rat is not responsive to glucagon during gestation and that responsiveness to glucagon and the associated ability of glucagon to deplete myocardial glycogen do not develop until well after birth.
When Is a Tumor Marker Not a Tumor Marker?
Authors: Judith L. Vaitukaitis
Journal: New England Journal of Medicine (1975)

Almost all the biologically active protein and polypeptide hormones, including those synthesized and secreted by the normal placenta, have been implicated in ectopic humoral syndromes associated with a wide variety of tumors in women and men.1 , 2 With the introduction of more sophisticated and sensitive technics, tumor extracts and serums of patients with a variety of neoplasms contained not only biologically inactive forms of hormones, but also altered chemical forms, ranging from incompletely synthesized to larger forms of the native hormone termed "prohormones."1 , 2 When chemically analyzed, those altered forms have not differed from fragments or prohormonal forms of the native hormones . . .
Azathioprine and Varicella
Authors: Richard N. Fine
Journal: JAMA (1969)

Clinical and serologic evidence of varicella developed in an 8-year-old boy while he was receiving azathioprine and steroids for immunosuppression 16 months after renal homotransplantation. The clinical course was benign, and no adverse effects on renal function were observed in relation to the clinical varicella.
Lack of Increased Coronary Atherosclerotic Risk Due to Elevated Lipoprotein(a) in Women ≥55 Years of Age
Authors: Satoshi Sunayama, Hiroyuki Daida, Hiroshi Mokuno, Hiroshi Miyano, Hisashi Yokoi, Young Joon Lee, Hidehiko Sakurai, Hiroshi Yamaguchi
Journal: Circulation (1996)

Background Numerous studies have indicated that there is an association between lipoprotein(a) [Lp(a)] and coronary artery disease (CAD) in middle-aged men; however, few studies have addressed this issue in women or the elderly. Methods and Results Serum Lp(a) concentrations were determined in 354 women and 706 men with or without angiographically defined CAD (one or more coronary arteries with narrowing of ≥75%). The age-specific impact of elevated Lp(a) (≥30 mg/dL) on CAD was examined in each sex. In the younger age group (&lt;55 years old), elevated Lp(a) was independently associated with CAD in both sexes (adjusted odds ratio [OR]: women, 6.90, P &lt;.01; men, 2.63, P &lt;.05). The age-specific ORs declined with age, and elevated Lp(a) no longer conferred an increased CAD risk in either elderly men or women ≥65 years old. In the age group of 55 to 64 years, elevated Lp(a) was positively associated with CAD for men (adjusted OR: 2.45, P &lt;.05) but not for women (adjusted OR: 0.56, P =NS). Conclusions For both sexes, elevated Lp(a) appears to be an independent risk factor for premature CAD and the importance of Lp(a) appears to decrease with age. However, for women, the risk estimate of Lp(a) began to decline at an age ≈10 years younger than for men. These data suggest that not only age- but also sex-specific factors such as menstrual status may interact with the association between Lp(a) and CAD.
Q Fever during Pregnancy -- A Risk for Women, Fetuses, and Obstetricians
Authors: Didier Raoult, Andreas Stein
Journal: New England Journal of Medicine (1994)

To the Editor: The pathogenic role of Coxiella burnetii during pregnancy is controversial. In cattle, sheep, and goats it has been suspected of causing abortion, low birth weight, and prematurity. Cases of Q fever have occasionally been reported during pregnancy in humans1. We report a case of infection during pregnancy, which was followed by fetal infection and death. A 26-year-old nurse who was eight weeks pregnant and worked in an intensive care unit presented with fever and cough. A diagnosis of acute Q fever was made on the basis of seroconversion, and she received co-trimoxazole for 21 days. She . . .
Prospective survey of use of therapeutic drugs, alcohol, and cigarettes during pregnancy.
Authors: P C Rubin, G F Craig, K Gavin, D Sumner
Journal: BMJ (1986)

Use of drugs during pregnancy was recorded prospectively in 2765 women attending the antenatal clinics of a general hospital from October 1982 to March 1984. Of these women, 2588 (93.6%) avoided exposure to drugs during the first trimester, 1802 (65.2%) took no drugs at any stage, 963 (34.8%) took a total of 154 different drugs from 35 groups of drugs, and 243 (8.8%) took a self administered drug. The most commonly used drugs were non-narcotic analgesics, usually self administered, and antibacterials. The last survey of use of drugs in pregnancy in the United Kingdom 20 years ago showed fewer women avoiding drugs throughout pregnancy (195 of 911 (21.4%), p less than 0.001) and in taking a self administered drug (586 (64.4%), p less than 0.001) than at present. Most women nowadays abstain totally from alcohol (1786 (64.6%) v 109 (12.0%) previously, p less than 0.001), but while more women are non-smokers compared with previously (1811 (65.5%) v 392 (43%), p less than 0.001) the trend has been far less dramatic than that for use of alcohol.
Indian court says it may sanction euthanasia in the future
Authors: G. Mudur
Journal: BMJ (2011)

India’s Supreme Court has declared that withdrawing life support to patients may be permitted in certain situations through a legal procedure, in a landmark ruling that the country’s medical community believes will provide guidance for care at the end of life.

On 7 March the court rejected a petition filed two years ago to withdraw feeding support from Aruna Shanbaug, a former nurse at the King Edward Memorial Hospital in Mumbai (Bombay), who has been in a persistent vegetative state since she was sexually attacked by a hospital cleaner in November 1973. But the court signalled that it would not rule out sanctioning some cases of euthanasia in the future if doctors approached the courts to request permission.

When she was attacked, …
The hospitals we need.
Authors: I S Loudon
Journal: BMJ (1976)

The hospitals we need SIR,-The report by Rickard,' based on a detailed and authoritative analysis of the cost-effectiveness of two community hospitals, demonstrates clearly how difficult it is to carry out cost-effective studies that allow valid comparisons to be made between two different kinds of hospital such as community hospitals and district general hospitals.As a result of this study Rickard came to the con- clusion (p 113) that "the cost oftreating medical patients in the Community Hospital . . .exceeded the district general hospital cost" and that "the policy implication of this part of the study is that the experimental community hospital units, as at present administered, are not cost-effective" (my italics).The study
Methoxamine Hydrochloride in the Treatment of Paroxysmal Supraventricular Tachycardia
Authors: L. A. Chotkowski, C. P. Powell, R. L. Rackliffe
Journal: New England Journal of Medicine (1954)

Recent reports1 , 2 in the literature have suggested that methoxamine (beta-[2.5-dimethoxyphenyl] beta-hydroxyisopropylamine) chloride,¶ a synthetic amine, is effective in terminating attacks of supraventricular tachycardia. To corroborate these observations, 3 cases are added to the 4 already reported. These 3 cases are of particular interest because continuous electrocardiograms were taken during the course of the attack during the administration of methoxamine hydrochloride. The electrocardiograms demonstrate a dramatic reversion of the paroxysmal to the normal rhythm in a matter of seconds. No attempt is made in this paper to compare the value of methoxamine hydrochloride with that of other established methods of treatment . . .
Diagnosis of Diabetic Gastroparesis on Tc-99m Hepatobiliary Scintigraphy
Authors: ALKA KUMAR, DIEU H. PHAM, HARRY MEINDOK, SHASHI AGGARWAL
Journal: Clinical Nuclear Medicine (1993)

Diabetic gastroparesis is a common problem in diabetics, especially insulin-dependent diabetics. The diagnosis usually is suggested on plain radiographs and confirmed on either upper gastrointestinal barium series or radionuclide gastric emptying studies. The clinical diagnosis is not always easy and some patients may present atypically with right upper quadrant pain simulating acute cholecystitis. In these patients, hepatobiliary scintigraphy may be the initial investigation performed and may first demonstrate unsuspected gastroparesis. Therefore, it is useful for the nuclear medicine physician to be aware of this entity to ensure early diagnosis and prompt treatment. The authors report one such case of diabetic gastroparesis that was diagnosed initially on a Tc-99m hepatobiliary scan.