tbuckley/cabot-search huggingface dataset:
THE POPULATION-DEPENDENT REQUIREMENT BY CULTURED MAMMALIAN CELLS FOR METABOLITES WHICH THEY CAN SYNTHESIZE
Authors: Harry Eagle, Karl Piez
Journal: The Journal of Experimental Medicine (1962)

At least seven compounds synthesized by cultured cells in amounts which should suffice for sustained growth have nevertheless proved under certain conditions necessary for survival (asparagine, cystine, glutamine, homocystine inositol, pyruvate, serine). In every instance so far examined, that requirement has been population-dependent, disappearing at cell densities sufficiently large to bring the concentration in the medium and in the cellular pool to metabolically effective levels before the cells died of the specific deficiency. At population densities of less than 100 cells per ml, serine was required by all cultured cells so far studied. With more exigent strains, such as the RT6 strain of rabbit fibroblast and the P388 mouse leukemia, the serine requirement disappeared only at populations in excess of 50,000 and 150,000 cells per ml, respectively. The requirement for pyruvate by the latter cell as an alternative to serine also disappeared at that population density. In a cystine-free medium there were population-dependent requirements for cystine, homocystine, or serine, depending on the experimental conditions. With methionine and glucose as cystine precursors, the critical population density permitting cellular survival and growth was in excess of 200,000 cells/ml. The provision of homocystine as an intermediate reduced the critical population density to 10,000 to 60,000 cells/ml; with the further provision of serine, the critical cell concentration permitting growth was reduced to 50 to 500 cells/ml. Cells adapted to glutamic acid, and capable of utilizing it as a substitute for glutamine, nevertheless required exogeneous glutamine at cellular densities of less than 50,000 cells per ml. In some experiments, the provision of asparagine reduced the critical population density to 10,000 cells/ml, presumably because of its glutamine-sparing action. Inositol is required by most cell lines, despite their demonstrated capacity to synthesize it from glucose. With at least one cell line (HeLa), sustained growth was occasionally achieved in an inositol-free medium if the population density was maintained in excess of 240,000 cells/ml. The possible implications of these findings with respect to the loss of specific organ functions in dispersed cell culture are discussed.
Cardiovascular Disease among Veterans of World War II
Authors: Aaron H. Traum, Blanche B. Wilcox
Journal: New England Journal of Medicine (1946)

THERE are many gaps in the knowledge of heart disease, the leading cause of death among adults in the United States. To follow a case of cardiovascular disease from its earliest recognized manifestations throughout the lifetime of the patient may lead to a better understanding of such disease processes. Furthermore, there is a distinct need for more information concerning the natural history of circulatory disturbances that apparently commence or exhibit their first signs and symptoms in young adults. The relation of race, sex, age, place of residence and similar factors to various types of heart disease can best be appraised . . .
730. Cancer Specific Promoters for Gene Therapy of Small Cell Lung Cancer
Authors: Nina Pedersen, Mikkel W. Pedersen, Michael S. Lan, Thomas T. Poulsen, Hans S. Poulsen
Journal: Molecular Therapy (2005)

For small cell lung cancer (SCLC) there is currently no satisfactory treatment, wherefore development of novel modalities, such as gene therapy, is highly in demand. As SCLC is a disseminated disease, treatment must be administered systemically and therefore requires absolute targeting to the cancer cells. One way to achieve targeting is by expressing the therapeutic gene from highly active, cancer specific promoters. We have identified a number of genes highly and specifically expressed in SCLC (Pedersen et al., Cancer Res 63, p1943, 2003) and are analysing the regulatory regions of these genes to identify promoters which can be used for targeting.
Abnormal Pap Smears, ASCUS Still Ob/Gyn Puzzle
Authors: Karen Titus
Journal: JAMA (1996)

WHEN IT comes to the management of women with abnormal Papanicolau (Pap) smears, clinicians are likely to respond to questions about ASCUS—atypical squamous cells of undetermined significance—with a simple but telling phrase: "Don't ask us." While the term 'ASCUS' is used to define Pap smears containing squamous cells of abnormal appearance that do not meet the criteria for defined epithelial abnormalities, on a practical level the diagnosis represents an "I-don't-know" category, noted Ralph M. Richart, MD, in a presentation at the annual meeting of the American College of Obstetricians and Gynecologists. Consequently, an ASCUS diagnosis presents vexing problems for cytopathologists, obstetricians, and gynecologists. The ASCUS category is filled with a variety of patients: those with low-grade squamous intraepithelial lesions (LSIL), high-grade squamous epithelial lesions, and hidden invasive cancers. "ASCUS has become kind of a wastebasket, like Class 2 smears were years ago," says Raymond H. Kaufman, MD, a professor in
Eugenic Sterilization
Authors: Morton Birnbaum
Journal: JAMA (1961)

Eugenic sterilization is defined as sterilization of a person who is either mentally ill or mentally defective and will either severely handicap any future offspring through heredity or is unable to properly care for a child. When an institutionalized mentally disordered person of reproductive age reaches a stage when he is able to return to the community, 3 possibilities arise: 1) eugenic surgical sterilization; 2) eugenic institutional sterilization, where the patient is effectively sterilized by being kept in the institution; and 3) discharge without eugenic sterilization. 3 cases of patients discharged without sterilization are presented. A review of the law of eugenic surgical sterilization reveals that 22 states have laws that permit compulsory eugenic sterilization without patient consent. Even though a state does not specifically authorize eugenic sterilization, it does not mean that such a procedure cannot be done legally. However, fewer and fewer eugenic sterilizations are being performed. Decisions relating to sterilization more often are made by medical men than by judges. Medically, the Committee of the American Neurological Association for the Investigation of Eugenical Sterilization, in a report made 25 years ago, condemned on both medical and philosophical grounds widespread eugenic surgical sterilizations except in certain cases. Morally, the author believes that patients and physicians are incapable of acting as moral beings in dealing with the question of eugenic sterilization because of 1) lack of proper facilities to allow freedom of choice, and 2) lack of knowledge of available relevant facts. With respect to the 3 alternatives for dealing with mental patients who are capable of reproducing, the author asks: Is it morally just to sterilize a person without first offering adequate treatment, rehabilitation, and follow-up that a well-equipped institution could offer? Is it just to incarcerate a patient without offering the personnel and facilities for proper custodial and therapeutic care? Is it proper to discharge a person without sterilization without offering rehabilitation and follow-up that might lead to a better life? A study comparing the way the problem of sterilization is being handled in states with different approaches to the subject is proposed.
Neuroimaging dual task performance in youth after sports-related concussion: an fMRI study
Authors: Michelle L Keightley, Katia Sinopoli, Greg Wells, Jen-Kai Chen, Tim Taha, Alain Ptito
Journal: British Journal of Sports Medicine (2013)

Objective To identify the neural substrates of a dual-task paradigm and evaluate performance in concussed versus non-concussed youth 3–6 months post-injury. Design Standard structural (T 1 , T 2 , FLAIR, DTI) and functional (single-shot T 2 *-weighted pulse sequence with in-out spiral readout images) were collected using a 3 Tesla imaging system. fMRIstat was used to analyse the data. Setting Male participants 9–15 years of age were recruited from The Greater Toronto Hockey League and The Hospital for Sick Children via poster advertising. Subjects 13 concussed youth (mean age=12.61+1.55 years) and 14 control subjects (mean age 12.59±1.55 years). Intervention None. Outcome Measures Accuracy (ACC) and reaction time (RT) during (1) a 0–3 back visuospatial working memory task; (2) a two finger button pressing motor task and (3) dual-task cost associated with simultaneously performing the working memory and motor tasks. Results There were no significant group differences across single and dual-task conditions. Although both groups activated similar brain regions across tasks, concussed youth demonstrated significantly less percent BOLD change in the prefrontal cortex across all working memory task comparisons. Similar results were found during the 1 vs 0 back and 2 vs 0 back dual task conditions, but not for the 3 vs 0 back dual task condition. Conclusions Differences in brain function can be observed in youth who have sustained a single injury 3–6 months earlier. Further research is needed to identify the clinical correlates of these atypical activation patterns. Acknowledgements Canadian Institute of Health Research (CIHR) and Ontario Neurotrauma Foundation (ONF). Competing interests None.
Points: Biphasic sulphinpyrazone-warfarin interaction
Authors: A Girolami, L Schivazappa, F Fabris, M L Randi
Journal: BMJ (1981)

liams's letter (10 October, p 987) about the management of gastrointestinal bleeding, and agree entirely with your comment.I would take exception, however, to his last sentence, which implies that an "alcoholic binge" may lead to an upper gastrointestinal haemorrhage and that this does not require investigation.It is our experience that when alcoholic excess leads to a massive bleed there is usually a chronic underlying cause, and I would suggest that these patients most certainly should be investigated.
Acute respiratory failure secondary to chronic obstructive pulmonary disease treated in the intensive care unit: a long term follow up study
Authors: D Breen
Journal: Thorax (2002)

Traditionally, patients with acute respiratory failure due to chronic obstructive pulmonary disease (COPD) admitted to the intensive care unit (ICU) are believed to have a poor outcome. A study was undertaken to explore both hospital and long term outcome in this group and to identify clinical predictors.A retrospective review was carried out of consecutive admissions to a tertiary referral ICU over a 6 year period. This group was then followed prospectively for a minimum of 3 years following ICU admission.A total of 74 patients were admitted to the ICU with acute respiratory failure due to COPD during the study period. Mean forced expiratory volume in 1 second (FEV1) was 0.74 (0.34) l. Eighty five per cent of the group underwent invasive mechanical ventilation for a median of 2 days (range 1-17). The median duration of stay in the ICU was 3 days (range 2-17). Survival to hospital discharge was 79.7%. Admission arterial carbon dioxide tension (PaCO2) and APACHE II score were independent predictors of hospital mortality on multiple regression analysis. Mortality at 6 months, 1, 2, and 3 years was 40.5%, 48.6%, 58.1%, and 63.5%, respectively. There were no independent predictors of mortality in the long term.Despite the need for invasive mechanical ventilation in most of the study group, good early survival was observed. Mortality in the long term was significant but acceptable, given the degree of chronic respiratory impairment of the group.
Urinary Excretion of the Cancer-Related Glycoprotein EDCI: Effect of Chemotherapy
Authors: DANIEL RUDMAN
Journal: Annals of Internal Medicine (1977)

The effect of chemotherapy on the urinary excretion of a cancer-related glycoprotein labeled EDCI, recently isolated from the urine of a patient with acute myelocytic leukemia, has been studied by radioimmunoassay in eight cancer patients who were excreting 200 to 500 mg/day before treatment. In five patients, chemotherapy caused marked clinical improvement, and the glycoprotein disappeared from the urine within 10 days after chemotherapy began. In the two patients with solid tumor who responded to chemotherapy, disappearance of glycoprotein EDCI from the urine preceded clinical improvement by 1 to 2 months. Four of the five responsive patients relapsed within 6 months; in each instance, the glycoprotein reappeared in the urine (> 100 mg/day) 2 to 5 weeks before clinical relapse. Three patients were resistant to chemotherapy, and their urinary glycoprotein did not decline during chemotherapy. Measurement of urinary glycoprotein EDCI will be useful in rapidly ascertaining which drug will be effective in a cancer patient and in predicting relapse.
Abstract LB-160: ITRI-260, a promising candidate for treatment of acute myeloid leukemia
Authors: Chih-Peng Liu, Hsingjin Eugene Liu, On Lee, Chih-Hung Chen, Jui-Wen Huang, Ting-Shou Chen, Ching-Huai Ko, Ling-Mei Wang, Yen-Chun Chen, Hsiang-Wen Tseng, Ying-Chu Shih, Shu-Jiau Chiou, Yuan-Jang Tsai, Chrong-Shiong Hwang
Journal: Cancer Research (2010)

Abstract Acute myeloid leukemia (AML) is a highly malignant hematopoietic tumor characterized by an abnormal proliferation of myeloid progenitor cells, decreased rate of self-destruction and an arrest in cell differentiation. The internal tandem duplication mutations of FMS-like tyrosine kinase-3 (FLT3/ITD mutations) are common in AML and linked to poor prognosis. ITRI-260 generated from designed by computer-assisted rationale drug design and in silico prioritized approaches, was proved to be a potent cell growth inhibitor against FLT3/ITD mutated AML cells through FLT3 and c-Kit inhibition. The in vivo efficacy of ITRI-260 via oral route was demonstrated in MV4-11 xenograft mice model. Besides, two more orthotopic murine models were used to assess the in vivo therapeutic efficacy of ITRI-260. The first one is MV4-11 cell orthotopically engraft into NOD/SCID mice bone marrow and the second one is primary AML cells from AML patient engraft into NOD/SCID mice bone marrow. The results show that ITII-260 can decrease FLT3/ITD mutant leukemia blasts in peripheral blood and bone marrow in both animal models. Finally, ITRI-260 prolongs the survival in both bone marrow engraft mice models. These findings strongly suggest clinical benefits of ITRI-260 in patients with FLT3/ITD AML. Currently we are planning the bridged projects to push ITRI-260 toward IND status. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-160.
Screening for genetic haemochromatosis in blood samples with raised alanine aminotransferase
Authors: M Bhavnani
Journal: Gut (2000)

In the UK approximately 1 in 140 people are homozygous for the C282Y mutation of the HFE gene and are at risk from iron overload caused by genetic haemochromatosis (GH). Early detection can prevent organ damage secondary to iron deposition and increase life expectancy.To screen for GH in all blood samples sent to the laboratory for routine liver function tests in which raised serum alanine aminotransferase (ALT) activity was detected.ALT was measured in sera sent to the laboratory for routine liver function tests. In those samples found to have raised activity, transferrin saturation and ferritin were measured followed by genetic testing when transferrin saturation was increased.Of the 35 069 serum samples assayed for routine liver function tests, 1490 (4.2%) had raised ALT levels (>50 u/l). Transferrin saturation and serum ferritin concentrations were measured in these patient samples, and in 56 transferrin saturation was >60%. Further blood samples were requested from these patients for genetic testing: 33 samples were obtained. There were nine patients homozygous for the C282Y mutation of the HFE gene and three compound heterozygotes (heterozygous for both C282Y and H63D mutations).The association of raised ALT activity and transferrin saturation of >60% could provide a simple, cost effective method for detecting individuals with clinical haemochromatosis. Although many patients with GH may have been missed, this study suggests that the clinical penetrance of the disorder may be much lower than is generally supposed and that genetic screening will identify many people who may never develop clinical haemochromatosis.
Unmasking of False-Negative Blood Cultures in Patients Receiving New Penicillins
Authors: Judith Carleton
Journal: JAMA (1963)

THE ORIGINAL INVESTIGATIONS of the new penicillinase-resistant penicillins demonstrated that their antimicrobial activity could be destroyed by sufficiently large concentrations of<i>Bacillus cereus</i>penicillinase.<sup>1</sup>During the course of experiments dealing with the bactericidal activity of such penicillins, it was essential to antagonize residual antibiotic in subcultures to avoid false-negatives. For this to be accomplished, the actual concentration of penicillinase necessary for this purpose had to be established. This information also could be extended to clinical laboratories where blood cultures are made from patients under treatment with these drugs. We have therefore investigated this problem via a study of ratios of<i>B cereus</i>penicillinase to penicillin required for inactivation of four penicillinase-resistant penicillins. For practical laboratory applications it is probably fortunate that<i>B cereus</i>penicillinase, which is easily obtainable, is more potent than staphylococcal penicillinase against resistant penicillins.<sup>1</sup>It is the purpose of this paper to report these studies.
Positive association of serum levels of advanced glycation end products with thrombogenic markers in humans
Authors: Mika Enomoto, Hisashi Adachi, Sho-ichi Yamagishi, Masayoshi Takeuchi, Kumiko Furuki, Asuka Hino, Akiko Hiratsuka, Yoshinori Takajo, Tsutomu Imaizumi
Journal: Metabolism (2006)
Neonatal Detection of Generalized Resistance to Thyroid Hormone
Authors: Roy E. Weiss
Journal: JAMA (1990)

Generalized resistance to thyroid hormone (GRTH) is an inherited disease that is usually suspected when elevated serum thyroid hormone levels are associated with nonsuppressed thyrotropin. Often these test results are obtained because of short stature, decreased intelligence, and/or hyperactivity with learning disability noted in childhood and adolescence, or because of goiter in adulthood. We detected GRTH at birth by analysis of blood obtained during routine neonatal screening. The proposita, born to a mother with GRTH, had a thyrotropin level of 26 mU/L and a corresponding thyroxine concentration of 656 nmol/L (normal, 84 to 232 nmol/L). Administration of thyroid hormone in doses eightfold to 10-fold above replacement levels (liothyronine sodium, 21 micrograms/kg per day, and levothyroxine sodium, 44 micrograms/kg per day) were required to reduce serum thyrotropin to normal levels without induction of hypermetabolism. This case, and the retrospective finding of high thyroxine levels in five newborns subsequently diagnosed as having GRTH, suggest that measurement of thyroxine at birth, in conjunction with thyrotropin, could allow the early detection of GRTH.
The Effect of Exercise on Coronary Blood Flow, Myocardial Oxygen Consumption and Cardiac Efficiency in Man
Authors: THOMAS A. LOMBARDO, LEONARD ROSE, MAX TAESCHLER, S. TULUY, R. J. BING
Journal: Circulation (1953)

It has been known that exercise causes an increase in the coronary blood flow in animals. The present work has been carried out to study the effect of exercise on coronary blood flow and myocardial oxygen consumption of the human heart in vivo. The results indicate that the heart responds to the increased load of exercise with a rise in coronary blood flow. Since the arteriovenous coronary oxygen difference shows little change, the increase in oxygen consumption of the heart muscle is primarily the result of an increased coronary blood flow. As the cardiac work rises more than the myocardial oxygen consumption, the left ventricular efficiency increases. The response of the failing heart muscle to acute increases in load produced by exercise does not differ from that of the normal heart or of the isolated heart.
Role of the time factor in signaling specificity: Application to mitogenic and metabolic signaling by the insulin and insulin-like growth factor-I receptor tyrosine kinases
Authors: Pierre De Meyts, Claus T. Christoffersen, Birgitte Ursø, Brenda Wallach, Karen Grønskov, Fumiatsu Yakushiji, Ronald M. Shymko
Journal: Metabolism (1995)
Nick Clegg promises to end "discrimination against mental health for good"
Authors: Z. Kmietowicz
Journal: BMJ (2014)

The deputy prime minister, Nick Clegg, has promised to put mental health on a par with physical health by setting targets for initiation of treatment for the first time from next April. Mental health services will also receive a funding boost of £120m (€152m; $193m) over the next two years, he said.

Clegg said that, from April 2015, three quarters of people with depression and anxiety who need talking therapy will start treatment within six weeks and that 95% will be seen within 18 weeks. And for people experiencing psychosis for the first time, the target from next April will be to start treatment within two weeks of referral, he said—giving severe mental illness the same priority targets as cancer. 

The aim is to increase this proportion in the coming …
Treatment of Status Epilepticus
Authors: Damon M. Fellman
Journal: JAMA (1994)

<h3>To the Editor.</h3> —As a practicing neurologist, I found the article by the Working Group on Status Epilepticus<sup>1</sup>valuable and detailed. However, I must comment on the recommendation that the decision to initiate long-term therapy should be individualized. The authors state that anticonvulsant treatment is prescribed by many neurologists following status epilepticus, though the decision is not supported by epidemiologic data. Epidemiologic data on recurrence of seizures depends on the likelihood that patients will report further seizures. Patients may avoid reporting seizures for several reasons (eg, loss of driver's license, fear of restrictions on other activities, or fear that more medication will be prescribed); therefore, existing data on how many patients who experience status epilepticus will have further seizures later in life are suspect. Underreporting seizures is likely. The epidemiologic data may not be definitive from this viewpoint. A crucial consideration is the likelihood that the patient will sustain