tbuckley/cabot-search huggingface dataset:
Noncoding sequences from the slowly evolving chloroplast inverted repeat in addition to rbcL data do not support gnetalean affinities of angiosperms
Authors: V. Goremykin, V. Bobrova, J. Pahnke, A. Troitsky, A. Antonov, W. Martin
Journal: Molecular Biology and Evolution (1996)

We developed PCR primers against highly conserved regions of the rRNA operon located within the inverted repeat of the chloroplast genome and used these to amplify the region spanning from the 3' terminus of the 23S rRNA gene to the 5' terminus of the 5S rRNA gene. The sequence of this roughly 500-bp region, which includes the 4.5S rRNA gene and two chloroplast intergenic transcribed spacer regions (cpITS2 and cpITS3), was determined from 20 angiosperms, 7 gymnosperms, and 16 ferns (21,700 bp). Sequences for the large subunit of ribulose bisphosphate carboxylase/oxygenase (rbcL) from the same or confamilial genera were analyzed in both separate and combined data sets. Due to the low substitution rate in the inverted repeat region, noncoding sequences in the cpITS region are not saturated with substitutions, in contrast to synonymous sites in rbcL, which are shown to evolve roughly six times faster than noncoding cpITS sequences. Several length polymorphisms with very clear phylogenetic distributions were detected in the data set. Results of phylogenetic analyses provide very strong bootstrap support for monophyly of both spermatophytes and angiosperms. No support for a sister group relationship between Gnetales and angiosperms in either cpITS or rbcL data was found. Rather, weak bootstrap support for monophyly of gymnosperms studied and for a basal position for the aquatic angiosperm Nymphaea among angiosperms studied was observed. Noncoding sequences from the inverted repeat region of chloroplast DNA appear suitable for study of land plant evolution.
Long-Term Use of Intranasal Insulin in Insulin-Dependent Diabetic Patients
Authors: Albert G Frauman, Mark E Cooper, Barry J Parsons, George Jerums, William J Louis
Journal: Diabetes Care (1987)

This study, in 3 phases, compared the long-term acceptability and efficacy of insulin administered by nasal spray with an intensified subcutaneous regimen in nine type I (insulin-dependent) diabetic subjects on baseline therapy with ultralente insulin. In phase 1, patients were begun and stabilized on a regimen of ultralente daily and Actrapid insulin three times daily. Phase 2 consisted of 4 mo of this intensified subcutaneous regimen. In phase 3, intranasal administration of insulin, with 1% (wt/vol) sodium glycocholate, replaced Actrapid insulin for 4 mo. Glycemic control was compared in each of the three phases. It was possible to maintain the dose of ultralente insulin relatively constant in only six of the nine subjects during the intranasal phase of the study. The six subjects showed a significant rise in glycosylated hemoglobin during the intranasal phase (10.4 ± 0.6% intranasal vs. 9.1 ± 0.3% subcutaneous, P &amp;lt; .05) but not in plasma or urinary glucose levels. There was no significant change in the incidence of hypoglycemic episodes during intranasal insulin therapy in this group. The other three subjects were considered treatment failures. Six of the nine original subjects expressed a preference for intranasal insulin, and one subject complained of mild nasal irritation insufficient to cease treatment. The intranasal route of administration of insulin has the potential to replace short-acting insulin as an adjunct to longer-acting insulin in some insulin-treated diabetic patients.
Egr-1 negatively regulates expression of the sodium?calcium exchanger-1 in cardiomyocytes in vitro and in vivo
Authors: C WANG, S DOSTANIC, N SERVANT, L CHALIFOUR
Journal: Cardiovascular Research (2004)

Objective: Increased expression of the transcription factor early growth response gene-1 (Egr-1) accompanies catecholamine infusion. Catecholamine-treated, Egr-1-deficient (−/−) mice show exacerbated cardiac damage when compared to similarly treated wild-type (+/+) mice, suggesting that Egr-1 reduces heart damage. We sought to identify Egr-1-mediated cardiac sparing genes.
The in-vitro and in-vivo effects of polyamines on cardiac protein biosynthesis
Authors: K. GIBSON, P. HARRIS
Journal: Cardiovascular Research (1974)

In cell-free systems putrescine, spermine, and spermidine at concentrations of 15 to 100 μg had no significant effect at 11 mM Mg2+ on rat myocardial aminoacyl-tRNA synthetase activity, transfer of amino acids from aminoacyl-tRNA into protein, or the incorporation of amino acid into protein using a myocardial ribosomal preparation. The polyamines stimulated cell free protein synthesis at low Mg2+ concentration. In the perfused rat heart, the addition of these polyamines to the perfusate increased the rate of incorporation of 14C-phenylalanine from the perfusate into myocardial protein. Spermine increased the uptake of α-aminoisobutyric acid into the myocardium of the perfused rat heart.
Ethical Issues in Growth Hormone Therapy
Authors: John Lantos, Mark Siegler, Leona Cuttler
Journal: JAMA (1989)

Pediatricians face clinical and ethical dilemmas about therapy to augment growth in short children who do not meet classic criteria for growth hormone (GH) deficiency. Biologic norms of health are unhelpful because of the uncertain relationship between stature, GH secretion, health, and disease. Instead, we suggest that GH therapy be evaluated from the perspective of cultural norms. We compare GH therapy for short normal children with currently accepted therapies for non--life-threatening pediatric conditions such as well-child care, cosmetic therapy, treatment of psychological problems, and invasive outpatient therapy for chronic conditions. Based on this analysis, we argue that the burdens of therapy, the uncertainty about long-term risks and benefits, the unclear therapeutic end point, and the implications for child health policy place routine GH therapy for children without documented deficiency of GH secretion outside current pediatric ethical norms. Such therapy is properly administered within a comprehensive clinical research protocol.Growth hormone therapy for short children who do not meet the classic criteria for growth hormone deficiency should be evaluated from the perspective of cultural values, not biologic norms of health. Physicians can weigh the ethical acceptability of new growth hormone therapies by comparing them with pediatric treatments for non-life-threatening problems, such as preventive well-child care, treatment for psychosocial problems, cosmetic therapy, and invasive outpatient therapy for chronic conditions. An analysis of the risks and benefits of growth hormone therapy and their implications for child health policy suggests that routine growth hormone therapy for children without documented deficiency of growth hormone secretion is properly administered within a comprehensive clinical research protocol and remains outside current pediatric ethical norms.
Alveolar Epithelial Fluid Transport Capacity in Reperfusion Lung Injury after Lung Transplantation
Authors: LORRAINE B. WARE, JEFFREY A. GOLDEN, WALTER E. FINKBEINER, MICHAEL A. MATTHAY
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Reperfusion lung injury is an important cause of morbidity and mortality after orthotopic lung transplantation. The purpose of this study was to investigate the function of the alveolar epithelium in the setting of reperfusion lung injury. Simultaneous samples of pulmonary edema fluid and plasma were collected from eight patients with severe post-transplantation reperfusion edema. The edema fluid to plasma protein ratio was measured, an indicator of alveolar–capillary barrier permeability. The initial edema fluid to plasma protein ratio was > 0.75 in six of eight patients, confirming the presence of increased permeability of the alveolar–capillary barrier. Graft ischemic time was positively correlated with the degree of permeability (r = 0.77, p < 0.05). In four of six patients with serial samples, there was a high rate of alveolar fluid clearance (19 ± 9%/h, mean ± SD). Alveolar fluid clearance was calculated from serial samples in six patients. Intact alveolar fluid clearance correlated with less histologic injury, rapid resolution of hypoxemia, and more rapid resolution of radiographic infiltrates. The two patients with no net alveolar fluid clearance had persistent hypoxemia and more severe histologic injury. This study provides the first direct evidence that increased permeability to protein is the usual cause of reperfusion edema after lung transplantation, with longer ischemic times associated with greater permeability to protein in the transplanted lung. The high rates of alveolar fluid clearance indicate that the fluid transport capacity of the alveolar epithelium may be well preserved in the allograft despite reperfusion lung injury. The ability to reabsorb fluid from the alveolar space was a marker of less severe reperfusion injury, whereas the degree of alveolar–capillary barrier permeability to protein was not. Measurement of alveolar fluid clearance may be useful to assess the severity of reperfusion lung injury and to predict outcome when pulmonary edema develops after lung transplantation.
Long Past Date Set for Its US Disappearance, Measles Remains a Threat to Many Children
Authors: Marsha F. Goldsmith
Journal: JAMA (1989)

AS THE SEVENTH anniversary of its target date for measles elimination in the United States—Oct 1, 1982—nears, the Centers for Disease Control (CDC), Atlanta, Ga, is preparing to investigate more than 20 deaths associated with the disease nationwide this year, more than in any year since the early 1970s. Lauri E. Markowitz, MD, a medical epidemiologist with the CDC's Division of Immunization, says the reasons for so many deaths are not fully understood. Moreover, she says, in the first 6 months of 1989, "we've had close to 90 outbreaks and more than 8000 cases of measles." This represents an increase of more than 300% over 1988. The 1989 number includes major outbreaks (&gt;100 cases) in Los Angeles, Calif, Houston, Tex, and Chicago, Ill, and lesser outbreaks in other areas across the country. At<i>JAMA</i>deadline, minor outbreaks were ongoing in at least half of the 50 states. "It's very frustrating," Markowitz
Influenza aerosols in UK hospitals during the influenza H1N1 (2009–10) pandemic: air sampling in the vicinity of patients undergoing WHO-defined aerosol generating procedures
Authors: Katy-Anne Thompson, John V Pappachan, Allan M Bennett, Himanshu Mittal, Susan Macken, Brian K Dove, Jonathan S Nguyen-Van-Tam, Vicky R Copley, Sarah O'Brien, Peter Hoffman, Simon Parks, Andrew Bentley, Barbara Isalska, Gail Thomson
Journal: The Lancet (2012)
Meta-analysis of the association between psoriasis and human leucocyte antigen-B
Authors: Y.E. Zhao, J.X. Ma, L. Hu, S.X. Xiao, Y.L. Zhao
Journal: British Journal of Dermatology (2013)

Currently there is no consensus about the association between psoriasis and human leucocyte antigen (HLA)-B.To clarify the association between psoriasis and HLA-B.Articles were selected, following predefined criteria, from case-control studies on the association between psoriasis and HLA-B published between 1 January 1972 and 11 November 2012, and included in the PubMed and ISI Web of Knowledge databases.Thirty-seven eligible articles covering 16 206 participants (14 644 white and 1562 Asian) were included. Sixty HLA-B alleles were reported, among which 26 were associated with susceptibility to disease, 24 were protective and 10 were unassociated. For unspecific psoriasis, there were three strongly susceptible alleles (OR ≥ 3·0) in white and four in Asian subjects, with HLA-B*57 and HLA-B*13 common to both races; there were four strongly protective (OR ≤ 0·3) alleles in white and seven in Asian subjects, with HLA-B*07 common to both. For psoriasis vulgaris, nine alleles were strongly associated with susceptibility in white subjects and five in Asians, with HLA-Bw*37 and HLA-B*57 in both; three alleles were strongly protective in white subjects and one in Asians, with none in common. Cases of psoriatic arthritis and guttate psoriasis were reported only in white subjects, with eight and seven strongly susceptible alleles, and two and three strongly protective alleles, respectively. Analyses of onset age showed that praecox patients with family history were significantly more susceptible to HLA-B*13 and HLA-B*57 than tardive ones.A significant association was identified between psoriasis and 50 HLA-B alleles. The association varied in terms of race, and clinical type and onset age of psoriasis.
FREQUENCY OF CORONARY ANGIOGRAPHY AND REVASCULARIZATION AMONG MEN AND WOMEN WITH MYOCARDIAL INFARCTION AND THEIR RELATIONSHIP TO MORTALITY AT ONE YEAR: AN ANALYSIS OF THE GEISINGER MYOCARDIAL INFARCTION COHORT
Authors: Kimberly A. Skelding, Peter B. Berger, James C. Blankenship, Vernon H. Mascarenhas, Christopher W. Good, Thomas D. Scott, John M. Hodgson
Journal: Journal of the American College of Cardiology (2010)
Abstract 3251: Blockade of HIF-1 with a small molecule inhibitor WP1066 in melanoma.
Authors: Arumugam Jayakumar, Jana Rauvolfova, Hanying Bao, Izabela Fokt, Stanislaw Skora, Amy Heimberger, Waldemar Priebe
Journal: Cancer Research (2013)

Abstract WP1066 was shown to exert its potent inhibitory activity against several types of human cancer including melanoma in vitro and in vivo via suppression of JAK2/STAT3/STAT5 activation. However, if there is any other additional molecular mechanism(s) by which WP1066 generates its anti-tumor effects remain largely unknown. Here, we report a novel function for WP1066 in inducing the degradation of both HIF-1α and HIF-1β subunits in human melanoma cells. We found constitutive activation of HIF-1α and an increased expression of hexokinase II, a down target of HIF-1α, in normoxia in 6/6 of melanoma cell lines, but not in other tumor types. Both hypoxia and cobalt chloride, a transition metal that mimics hypoxia, further increased HIF-1α protein accumulation in a time-dependent manner in WM35 and SKMEL-1 melanoma cells. WP1066 selectively decreased the constitutive and hypoxia and cobalt chloride induced increase in the level of HIF-1α in a dose-dependent manner with a half-life (T1/2) of ∼13, ∼10, and ∼10 min in WM35 cells. Moreover, WP1066 decreased the T1/2 of HIF-1α following cycloheximide treatment from ∼13 to ∼7 min suggesting that WP1066 induced HIF-1α instability is not mediated via inhibition of its translation. Further, inhibition of HIF-1α protein accumulation by WP1066 was not abolished in the presence of MG132 and proteasome inhibitor I, a potent inhibitor of the 26S proteasome, suggesting that the 26S proteasome-system is not responsible for WP1066-induced HIF-1α instability. Immunoprecipitation, confocal microscopy, and cellular fractionation analyses revealed that WP1066 induced ubiquitinylation, aggregation and degradation of HIF-1α in WM35 cells. Finally, WP1066 directly inhibits activity of rhUSP5 and rUCH-L1. Altogether, our study identified a novel function for WP1066 in inducing HIF-1 instability that may also contribute to the anti-cancer effects of WP1066 in human melanoma. Citation Format: Arumugam Jayakumar, Jana Rauvolfova, Hanying Bao, Izabela Fokt, Stanislaw Skora, Amy Heimberger, Waldemar Priebe. Blockade of HIF-1 with a small molecule inhibitor WP1066 in melanoma. [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 3251. doi:10.1158/1538-7445.AM2013-3251
Cumulative Association of Five Genetic Variants with Prostate Cancer
Authors: S. Lilly Zheng, Jielin Sun, Fredrik Wiklund, Shelly Smith, Pär Stattin, Ge Li, Hans-Olov Adami, Fang-Chi Hsu, Yi Zhu, Katarina Bälter, A. Karim Kader, Aubrey R. Turner, Wennuan Liu, Eugene R. Bleecker, Deborah A. Meyers, David Duggan, John D. Carpten, Bao-Li Chang, William B. Isaacs, Jianfeng Xu, Henrik Grönberg
Journal: New England Journal of Medicine (2008)

Single-nucleotide polymorphisms (SNPs) in five chromosomal regions--three at 8q24 and one each at 17q12 and 17q24.3--have been associated with prostate cancer. Each SNP has only a moderate association, but when SNPs are combined, the association may be stronger.We evaluated 16 SNPs from five chromosomal regions in a Swedish population (2893 subjects with prostate cancer and 1781 control subjects) and assessed the individual and combined association of the SNPs with prostate cancer.Multiple SNPs in each of the five regions were associated with prostate cancer in single SNP analysis. When the most significant SNP from each of the five regions was selected and included in a multivariate analysis, each SNP remained significant after adjustment for other SNPs and family history. Together, the five SNPs and family history were estimated to account for 46% of the cases of prostate cancer in the Swedish men we studied. The five SNPs plus family history had a cumulative association with prostate cancer (P for trend, 3.93x10(-28)). In men who had any five or more of these factors associated with prostate cancer, the odds ratio for prostate cancer was 9.46 (P=1.29x10(-8)), as compared with men without any of the factors. The cumulative effect of these variants and family history was independent of serum levels of prostate-specific antigen at diagnosis.SNPs in five chromosomal regions plus a family history of prostate cancer have a cumulative and significant association with prostate cancer.
Research misconduct—easy to suspect, hard to prove
Authors: Douglas Kamerow
Journal: BMJ (2007)

Academics and editors always chide clinicians for not practicing evidence based medicine. But what about when the evidence is possibly falsified? Take the case of neurosurgeon Julio Cruz, who authored papers from three clinical trials finding high dose mannitol infusions superior to conventional dosages in the treatment of head trauma (doi: 10.1136/bmj.39118.480023.BE). His studies were published in respected, peer reviewed journals in 2001-4 and included in a subsequent Cochrane systematic review endorsing the …
Toxic epidermal necrolysis associated with indapamide.
Authors: R J Black, P Murphy, T J Robinson, K W Scott
Journal: BMJ (1990)

injection of prostaglandin F,,, or hyperosmolar glucose can be used with considerable success.Prostaglandin F2,, increases tubal smooth muscle motility and causes powerful contractions,4 which explains its mode of action.Hyperosmolar glucose is thought to act as a noxious agent, dehydrating the cells and causing necrobiosis and thus ending the ectopic gestation.Although methotrexate and prostaglandins are associated with side effects, none were found when hyperosmolar glucose was used.'In this group subsequent hysterosalpingography showed that seven of the eight patients had normal tubal configuration and patency, and three later had a normal intrauterine pregnancy.
Further Careers of Young British Doctors
Authors: J. M. Last, E. Broadie
Journal: BMJ (1970)

After surveys in 1961 and 1966, further questionnaires were sent in 1969 to those who had responded in 1966. These showed that wastage due to emigration and unemployment of married women doctors was nearly 20%. Compared with 49% of all qualified for three to four years in 1966, 73% had definitely decided on their future career seven to eight years after qualifying in the 1969 survey, the choice tending to be for specialties less popular among more junior doctors. Responsibility for patient care seemed not to be related directly to seniority or to performance in medical school examinations.
Levels of lead and other metals in human blood: suggestive relationships, determining factors.
Authors: R L Zielhuis, P del Castilho, R F Herber, A A Wibowo
Journal: Environmental Health Perspectives (1978)

Epidemiological studies on metal levels in blood were carried out. Evidence suggested the existence of a different trend in serum-iron levels in relation to blood lead levels in nonoccupationally exposed males (negative trend) and females (positive trend). There was a positive relation between blood lead levels and blood manganese levels in children and occupationally exposed male workers. Blood metal levels increased with age in young children. There was evidence for an influence of socioeconomic class on blood lead levels in children. A direct and an indirect effect of smoking was found on blood lead levels and on the activity of delta-aminolevulinic acid dehydratase activity in erythrocytes in adult nonoccupationally exposed females.
Validation of the mantle cell lymphoma international prognostic index: A single‐center retrospective analysis
Authors: Stephen D. Smith, Eric Hsi, Brian Bolwell, Brad Pohlman, Robert Dean, Meagan Effinger, Amanda Maggiotto, John Sweetenham
Journal: American Journal of Hematology (2010)

Mantle cell lymphoma (MCL) is a unique, recently recognized entity with a variable clinical course [1]. Its historical grouping as an indolent lymphoma belies its common behavior, which is generally aggressive and incurable, with a median survival of about 5 years with modern therapy [2]. In an effort to improve outcomes in MCL, intensified therapies, including the rituximab plus HyperCVAD regimen [3] and incorporation of hematopoetic progenitor cell transplantation (HPCT) [4-6], have been used. However, although capable of inducing remissions in most patients, there is little proof that intensive first-line therapy prolongs overall survival (OS), and a continual relapse pattern is commonly observed [4,7-10].
Cardiopulmonary bypass. Microembolization and platelet aggregation.
Authors: R T Solis, P S Kennedy, A C Beall, G P Noon, M E DeBakey
Journal: Circulation (1975)

Particulate microemboli and in vitro platelet aggregation were studied in blood of patients during cardiac operations with an electronic particle size analyzer. A small gradient of microemboli developed on passage of blood through a bubble oxygenator but not through a membrane oxygenator. However, with both types of oxygenators, there was a sustained increase in the volume of microemboli in cardiotomy return blood which was much greater than in aterial blood. After cardiopulmonary bypass with both oxygenators, there was a comparable reduction in the volume of circulating platelets which exceeded that of the hemoglobin concentration, indicating platelet loss exceeded that that expected from hemodilution alone. However, the total volume and mean size of platelet aggregates induced in blood of patients after membrane oxygenation was significantly greater than similar measurements after bubble oxygenation. This study shows that membrane oxygenation reduces particulate microembolization and preserves platelet function in patients undergoing cardiac operations when compared to bubble oxygenation.