tbuckley/cabot-search huggingface dataset:
Evidence for a Postsecretory Reabsorptive Site for Uric Acid in Man
Authors: Herbert S. Diamond, James S. Paolino
Journal: Journal of Clinical Investigation (1973)

The effects of administration of drug combinations on uric acid excretion were studied in order to test the hypothesis that a portion of renal tubular reabsorption of uric acid occurs distal to the uric acid secretory site. Oral administration of pyrazinamide (3 g) during probenecid uricosuria (probenecid 500 mg every 6 h) decreased urate excretion from 463 mug/min following probenecid medication alone to 135 mug/min following probenecid plus pyrazinamide (P < 0.01). When a greater uricosuric effect was induced with a 2 g oral dose of probenecid, the decrement in urate excretion which followed pyrazinamide administration (3 g) was more pronounced (2,528 mug/min following probenecid alone, 574 mug/min following probenecid plus pyrazinamide). Results were similar when an 800 mg oral dose of sulfinpyrazone was given in place of probenecid (1,885 mug/min following sulfinpyrazone alone, 475 mug/min following sulfinpyrazone plus pyrazinamide). Thus, apparent urate secretion (measured as the decrease in excretion of urinary uric acid resulting from pyrazinamide administration) appeared to vary, depending upon the degree of inhibition of reabsorption produced by probenecid or sulfinpyrazone. When small doses of aspirin were administered in place of pyrazinamide to produce secretory inhibition, the results were similar. Neither probenecid nor pyrazinamide significantly altered urate excretion when administered to patients with serum salicylate levels above 14 mg/100 ml. These results are interpreted as suggesting that renal tubular reabsorption of uric acid occurs at least in part at a postsecretory site and that a portion of secreted urate is reabsorbed. During maximum probenecid- or sulfinpyrazone-induced uricosuria, inhibition of urate secretion with either pyrazinamide or low doses of aspirin resulted in a decrease in uric acid excretion which exceeded total urinary uric acid during control periods by two- to fourfold. This suggests that renal tubular secretion of urate may greatly exceed uric acid excretion and that a large fraction of secreted urate is reabsorbed. The pyrazinamide suppression test underestimates urate secretion. Uricosuria induced by some drugs, including probenecid, sulfinpyrazone, and iodinated radioopaque dyes, appears to represent, at least in part, inhibition of postsecretory urate reabsorption.
1030. A Rhesus Macaque Transplant Model for Drug Selection of Hematopoietic Stem Cells Transduced with MGMT Vectors
Authors: Yan Shou, John Gray, Brian Agricola, Zhijun Ma, Derek P. Persons, Brian P. Sorrentino
Journal: Molecular Therapy (2005)

Gene transfer of the DNA repair protein O6-methylguanine-DNA-methyltransferase (MGMT) into hematopoietic stem cells (HSCs) results in efficient in vivo selection of murine HSCs after treatment with temozolomide (TMZ) and O6-benzylguanine (BG). In addition, MGMT gene transfer into HSCs can protect hematopoiesis from the toxic side effects of chemotherapeutic agents in the treatment of malignant diseases. We are studying whether this drug resistance system will be efficacious in non-human primates using a rhesus macaque autologous transplantation model. In our first two transplant cases, we used an MSCV-P140K-IRES-GFP vector to transduce bone marrow cells that had been harvested after treatment with SCF and G-CSF, and then purified on a Miltenyi CliniMACS column using the anti-CD34 MoAb clone 563. Both animals engrafted after total body irradiation. The first animal showed relatively high levels of GFP+ B cells (40%) and lower levels of GFP+ granulocytes (3%) in the peripheral blood prior to treatment with 2 courses of TMZ and BG, 88 and 98 days after transplant. After the second course of drug selection, there was an increase in GFP+ granulocytes from 3% to a peak of 18%. These levels gradually declined back to baseline over the next 75 days. Subsequent treatment courses did not result in further selection. The second transplant case had less than 1% GFP+ granulocytes in the peripheral blood, probably due to an insufficient dose of total body irradiation, and no evidence of in vivo selection following drug treatment. In order to achieve higher levels of marking prior to selection, and to test whether inclusion of HOXB4 would improve the efficiency of selection, we developed a series of SIV vectors which co-expressed various combinations of P140K-MGMT, HOXB4, and GFP using the self-cleavage peptide 2A from porcine teschovirus-1 (P2A). A tricistronic SIV vector was constructed that incorporated all three genes by using different 2A sequences from the porcine teschovirus-1 and the asigna virus. Western blot analysis showed complete cleavage of each protein with no fusion proteins detected. We then generated amphotropic pseudotyped vectors with average titers ranging from 2 |[acute]| 105 to 1.2 |[acute]| 106 per milliliters on HeLa cells. Transduction of rhesus CD34+ cells with these SIV vectors resulted in around 40% GFP+ cells immediately after transduction for the MGMT-P2A-GFP vector and the MGMT-P2A-HOXB4-T2A-GFP vector, and about 20% marking for the HOXB4-P2A-GFP vector. In the presence of 800 mM TMZ, about 25% of CFU-C were drug resistant in vitro using the SIV vectors containing the MGMT expression cassette. For both vectors expressing HOXB4, expansion of GFP+ CD34+ cells was noted over 12-day in vitro cultures, with GFP+ cells increasing from 20% to 40% in most experiments. Our efforts are now focused on further evaluation of these SIV vectors in vivo, in transplanted rhesus macaques.
UK House of Lords rejects physician assisted suicide
Authors: Clare Dyer
Journal: BMJ (2006)

A bill to legalise physician assisted suicide was thrown out by the UK parliament's second chamber, the House of Lords, last week, after a day of impassioned debate. The private member's bill, tabled by the crossbench peer Joel Joffe, was derailed when peers voted 148 to 100 to delay it for six months.

The rarely used amendment to delay the bill was tabled by the Liberal Democrat peer and criminal lawyer Alex Carlile QC, who described the bill as “morally indefensible.”

The Assisted Dying for the Terminally Ill Bill, which would allow …
A novel SCFA receptor, the microbiota, and blood pressure regulation
Authors: Jennifer Pluznick
Journal: Gut Microbes (2013)

The maintenance of blood pressure homeostasis is a complex process which is carefully regulated by a variety of inputs. We recently identified two sensory receptors (Olfactory receptor 78 and G protein couple receptor 41) as novel regulators of blood pressure. Both Olfr78 and Gpr41 are receptors for short chain fatty acids (SCFAs), and we showed that propionate (a SCFA) modifies blood pressure in a manner which is differentially modulated by the absence of either Olfr78 or Gpr41. In addition, propionate modifies renin release in an Olfr78-dependent manner. Our study also demonstrated that antibiotic treatment modulates blood pressure in Olfr78 null mice, indicating that SCFAs produced by the gut microbiota likely influence blood pressure regulation. In this addendum, we summarize the findings of our recent study and provide a perspective on the implications of the interactions between the gut microbiota and blood pressure control.
Thalassaemia in the British
Authors: H. H. M. Knox-Macaulay, D. J. Weatherall, J. B. Clegg, M. E. Pembrey
Journal: BMJ (1973)

Different forms of thalassaemia or related disorders were found in 116 people of apparently pure British stock. Among them were one family with a child homozygous for beta-thalassaemia and eight heterozygous relatives, 16 families with 83 persons heterozygous for beta-thalassaemia, two families with three persons with Hb H disease and three heterozygous for alpha-thalassaemia 1, one family with a child apparently homozygous for the "silent beta-thalassaemia gene," one family with six members heterozygous for a form of beta-thalassaemia intermedia, and three families with 11 members heterozygous for different types of hereditary persistence of fetal haemoglobin. The clinical, haematological, and haemoglobin biosynthetic findings in these persons were similar to those of patients with thalassaemia from other racial groups. The heterozygous state for beta-thalassaemia is overlooked in British patients, particularly during pregnancy, because it is not considered in the differential diagnosis of refractory anaemia. In many cases this leads to much unnecessary investigation and potentially harmful treatment.There seem to be several varieties of hereditary persistence of fetal haemoglobin production among British people. These conditions, while not causing anaemia, may cause difficulties during examination of maternal blood for fetal cells and may, if inherited with a beta-thalassaemia gene, produce an unusually high level of Hb F in a person heterozygous for beta-thalassaemia.
Three types of health education.
Authors: P Draper, J Griffiths, J Dennis, J Popay
Journal: BMJ (1980)

Abstract: Types of health  in Britain may be categorized as personal physical health and maintenance, the use of health care resources, and the importance of the environment to public health. The latter category is relevant to policy-making in many areas: public transport, agriculture, economic growth, smoking (and tax revenues), job safety, etc. While national policy should be based on and be responsive to these concerns, the community development approach to health education, as practiced recently in developing countries and in the U.S., must not be overlooked. Public health programs must involve social change and overcoming the status quo; this process is sometimes impeded by the psuedo-health education of commercial enterprises. The interests of the public would best be served through integration of all 3 types of health education.
High Court upholds right of woman to travel abroad for suicide
Authors: Clare Dyer
Journal: BMJ (2004)

A 65 year old British woman with a degenerative brain condition committed suicide at a Zurich clinic this month, after a High Court judge refused to intervene to stop her husband taking her there.

Suicide is not a crime in Britain, but aiding a suicide is a serious offence carrying a maximum 14 year prison term. The judge, Mr Justice Hedley, said that the husband, named only as Mr Z, had arguably already committed the crime by the time the case came to court, in arranging for his wife to make …
Integration of Retroviruses: A Fine Balance between Efficiency and Danger
Authors: Alain Fischer, Marina Cavazzana-Calvo
Journal: PLoS Medicine (2005)

0022 One of the key characteristics of retroviruses is their ability to integrate a copy of the DNA reverse-transcribed from their viral RNA genome into host cell DNA. This integration is mediated by a preintegration complex (PIC) comprising viral DNA, reverse transcriptase, and integrase, as well as poorly characterized host proteins [1]. It is this property that makes retroviruses good vectors for the transfer of therapeutic genes, and many such vectors have been made.
EFFICACY OF LOW DOSES OF HEPARIN IN PREVENTION OF DEEP-VEIN THROMBOSIS AFTER MAJOR SURGERY
Authors: V.V. Kakkar, J. Spindler, P.T. Flute, T. Corrigan, D.P. Fossard, R.Q. Crellin, S. Wessler, E.T. Yin
Journal: The Lancet (1972)
Relief versus development
Authors: S. Gibbs, A. Latham
Journal: BMJ (1995)

It is now well over a year since the refugees came from Rwanda. Thereare currently about 450000 of them. The original population of this remote and rather inaccessible district of Tanzania was just under 200000. Before April 1994 Ngara was a quiet backwater of typical African rural under-development. Most people were subsistence farmers cultivating exclusively by hand and enduring ordinary day to day poverty with great equanimity.

In the past year or so the district hospital (in which both of us have been working for the past five years), in keeping with government policy, has been obliged to introduce charges for patients. According to the stipulations of structural adjustment Tanzanians can no longer enjoy the luxury of free health care. Our charges are high enough to deter many patients but far too low to realistically run a district hospital. Ngara has been connected to the 20th century and, as its agricultural economy is essentially mediaeval, there are going to be problems.

The events of April 1994 and their aftermath have provided further food for thought, however, and it is surprisingly indigestible. The sudden appearance of several hundreds …
Incomplete redistribution in delayed thallium-201 single photon emission computed tomographic (SPECT) images: An overestimation of myocardial scarring
Authors: Karen G. Cloninger, E.Gordon DePuey, Ernest V. Garcia, Gary S. Roubin, Wendy L. Robbins, Agatha Nody, Eugene E. DePasquale, Harvey J. Berger
Journal: Journal of the American College of Cardiology (1988)
Erratum to ‘Peptide-mediated intracellular delivery of miRNA-29b for osteogenic stem cell differentiation’ [Biomaterials 34 (2013) 4347–4359]
Authors: Jin Sook Suh, Jue Yeon Lee, Young Suk Choi, Chong Pyoung Chung, Yoon Jeong Park
Journal: Biomaterials (2014)
Atypical Presentation of Plasma Cell Leukemia Secondary to Multiple Myeloma Detected by F-18 FDG PET/CT
Authors: Fabrizio Cocciolillo, Giorgio Treglia, Maria Felicia Villani, Alessandro Giordano
Journal: Clinical Nuclear Medicine (2011)

We report a case of atypical muscle localization of plasma cell leukemia (PCL), arisen from a secondary leukemic transformation of multiple myeloma (MM), detected by F-18 FDG PET/CT. A 57-year-old woman with a history of MM received chemotherapy and hematopoietic stem cell transplantation with complete treatment response. Five years later, the patient presented a recurrence of MM and an evolution in PCL. F-18 FDG PET/CT showed areas of increased radiopharmaceutical uptake in some muscles of the right leg and right thigh, corresponding to muscle localization of PCL, therefore allowing adequate treatment planning.
Quality of life monitoring in ambulatory heart failure patients: temporal changes and prognostic value
Authors: Josep Lupón, Paloma Gastelurrutia, Marta de Antonio, Beatriz González, Lucía Cano, Roser Cabanes, Agustín Urrutia, Crisanto Díez, Ramón Coll, Salvador Altimir, Antoni Bayes‐Genis
Journal: European Journal of Heart Failure (2012)
Selectins and their counter receptors: a bitter sweet attraction.
Authors: F A Symon, A J Wardlaw
Journal: Thorax (1996)

Selectins are adhesion receptors expressed by leucocytes, platelets, and endothelial cells. They mediate the initial binding of leucocytes to vascular endothelium in the post-capillary venules. This is an essential first step in leucocyte migration into tissue. The selectin family of adhesion receptors consists of three C-type lectins (E, P, and L selectin). Their ligands (counter structures) are sialylated and fucosylated carbohydrate molecules which, in most cases, decorate mucin-like glycoprotein membrane receptors. Studies using blocking monoclonal antibodies have shown that inhibition of selectin function can ameliorate a range of inflammatory processes, offering the possibility that antagonists of selectin function may be useful in the treatment of inflammatory lung diseases such as asthma.
A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia
Authors: Daniel Herranz, Alberto Ambesi-Impiombato, Teresa Palomero, Stephanie A Schnell, Laura Belver, Agnieszka A Wendorff, Luyao Xu, Mireia Castillo-Martin, David Llobet-Navás, Carlos Cordon-Cardo, Emmanuelle Clappier, Jean Soulier, Adolfo A Ferrando
Journal: Nature Medicine (2014)
Identification of sources of lead in children in a primary zinc-lead smelter environment.
Authors: Brian L Gulson, Karen J Mizon, Jeff D Davis, Jacqueline M Palmer, Graham Vimpani
Journal: Environmental Health Perspectives (2003)

We compared high-precision lead isotopic ratios in deciduous teeth and environmental samples to evaluate sources of lead in 10 children from six houses in a primary zinc-lead smelter community at North Lake Macquarie, New South Wales, Australia. Teeth were sectioned to allow identification of lead exposure in utero and in early childhood. Blood lead levels in the children ranged from 10 to 42 micro g/dL and remained elevated for a number of years. For most children, only a small contribution to tooth lead can be attributed to gasoline and paint sources. In one child with a blood lead concentration of 19.7 microg/dL, paint could account for about 45% of lead in her blood. Comparison of isotopic ratios of tooth lead levels with those from vacuum cleaner dust, dust-fall accumulation, surface wipes, ceiling (attic) dust, and an estimation of the smelter emissions indicates that from approximately 55 to 100% of lead could be derived from the smelter. For a blood sample from another child, > 90% of lead could be derived from the smelter. We found varying amounts of in utero-derived lead in the teeth. Despite the contaminated environment and high blood lead concentrations in the children, the levels of lead in the teeth are surprisingly low compared with those measured in children from other lead mining and smelting communities.
PREDICTORS AND CARDIOVASCULAR PROGNOSIS OF INCIDENT AND PERSISTENT RESISTANT HYPERTENSION: A 4-YEAR FOLLOW-UP STUDY
Authors: Konstantinos P. Tsioufis, Alexandros Kasiakogias, Athanasios Kordalis, Kyriakos Dimitriadis, Konstantinos Kintis, Dimitris Flessas, Anastasia Mazaraki, Lefki Nikolopoulou, Evagelia Koutra, Panagiota Valenti, Bogianka Kostantinova-Gaki, Dimitris Tousoulis, Christodoulos I Stefanadis
Journal: Journal of the American College of Cardiology (2014)
The Fungous Diseases of Man
Authors: George L. Fite
Journal: JAMA (1966)

Although interest in medical mycology stimulates the production of a new text with consistent regularity every three to four years, this latest contribution presents some features omitted by others.  Two of these deserve particular notice. One is the inclusion of a substantial section on the morphology of fungi, especially those pathogenic for man. Nothing is more frustrating to the student of medical mycology, seeking to go a little more deeply into the molds and slimes, than to discover the superficial treatment given by existent medical texts. Like other disciplines, mycology owns a delirious terminology, for which a glossary (as supplied) is essential to the neophyte. In the broad sense, cleistothecial initials composed of clavate antheridium surrounded by coiled ascogonium describes an attribute of a fungus known in its conidial state as Microsporum gypseum ! Although laboratory workers usually have little interest in the organisms beyond establishment of diagnosis, there will be
Abstract 1126: Efficacy of BET bromodomain inhibition in Kras-positive non-small cell lung cancer.
Authors: Takeshi Shimamura, Zhao Chen, Margaret Soucheray, Julian Carretero, Eiki Kikuchi, Jeremy H. Tchaicha, Yandhi Gao, Katherine A. Cheng, Travis J. Cohoon, Jun Qi, Esra A. Akbay, Alec C. Kimmelman, Andrew L. Kung, James E. Bradner, Kwok Kin Wong
Journal: Cancer Research (2013)

Abstract Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as dependency of Kras-dependent tumors on c-Myc function. Unfortunately, drug-like small-molecule inhibitors of KRAS and c-Myc have yet to be realized. The recent discovery in hematologic malignancies that bromodomain inhibition impairs MYC expression and MYC-dependent transcriptional function prompted the possibility of targeting KRAS-driven NSCLC with a potent, prototypical BET bromodomain inhibitor, JQ1. Here, we report that NSCLC cells harboring the KRAS mutation are sensitive to JQ1 while NSCLC cells with concurrent mutant KRAS and LKB1 mutations are resistant to JQ1. In sensitive NSCLC models, JQ1 treatment results in the coordinate downregulation of the MYC-dependent transcriptional program. Furthermore, we evaluated JQ1 in transgenic mouse lung cancer models expressing mutant kras or concurrent mutant kras and lkb1. We found that JQ1 treatment produces significant tumor regression in mutant kras mice. As predicted, tumors from mutant kras and lkb1 mice did not respond to JQ1. Together, these data provide a compelling rationale for the study of BET bromodomain inhibitors in a common, genetically-defined population of patients with aggressive NSCLC. Citation Format: Takeshi Shimamura, Zhao Chen, Margaret Soucheray, Julian Carretero, Eiki Kikuchi, Jeremy H. Tchaicha, Yandhi Gao, Katherine A. Cheng, Travis J. Cohoon, Jun Qi, Esra A. Akbay, Alec C. Kimmelman, Andrew L. Kung, James E. Bradner, Kwok Kin Wong. Efficacy of BET bromodomain inhibition in Kras-positive non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1126. doi:10.1158/1538-7445.AM2013-1126
CULTURAL EDUCATION OF A PHYSICIAN
Authors: WILLIAM W. ROOT
Journal: JAMA (1942)

In an address delivered at the commencement of the Medical School of Harvard University at the Medical College in Boston, March 9, 1870 the Honorable Preston Peabody<sup>1</sup>spoke to the graduating class; he stressed particularly the importance of general culture: To your professional knowledge you need to add general culture as wide and thorough as your special studies and labors will permit. You owe this to yourselves, to your brethren, to your calling. You owe it to yourselves; for the man who confines himself to a single department, however noble it may be, sacrifices his own intellectual manhood; moves, not in a self-returning circle, but in a constantly diminishing spiral, and from year to year becomes less, and not beautifully less. You have a vital interest in poetry, literature and art—in all that is beautiful and grand in the works of God and man. You need them for recreation,
Does Hemoglobin Breathe, and If Yes, How? — The T and R State of Hemoglobin
Authors: K. H. Winterhalter
Journal: New England Journal of Medicine (1973)

Most mammalian hemoglobins consist of two unlike pairs of polypeptide chains, each one carrying a heme molecule. For the adult human erythrocyte more than 90 per cent of its hemoglobin content is hemoglobin A, which consists of two α and two β chains (hemoglobin A2 [two alpha and two delta chains] accounts for about 2.5 per cent of normal adult hemoglobin, and hemoglobin F [two alpha and two gamma chains] for less than 1 per cent). The α chain has 141, and the β chain 146 amino acids in a specific sequence, which is termed the "primary structure." On . . .
Research on Psychosocial Adjustment of Indian Youth
Authors: HARRY L. SASLOW, MAY J. HARROVER
Journal: American Journal of Psychiatry (1968)

The school experiences of Indian children tend to accentuate rather than resolve their identity problems; the outcome is often an increase in behavioral and disciplinary difficulties. At some point between the fourth and seventh grades a decline in academic achievement sets in, and the typical Indian student falls progressively behind his Anglo-American counterpart. The authors conclude that effective educational programs for American Indian youth must emphasize the development of adequate psychosocial adjustment.