tbuckley/cabot-search huggingface dataset:
Localization and characterization of a novel secreted protein SCUBE1 in human platelets
Authors: C TU, Y SU, Y HUANG, M TSAI, L LI, Y CHEN, C CHENG, D DAI, R YANG
Journal: Cardiovascular Research (2006)

The aim of the study was to investigate the protein expression and function of a novel secreted protein in the vascular system, named SCUBE1 for signal peptide, CUB (Complement proteins C1r/C1s, Uegf, and Bmp1) and epidermal growth factor-like (EGF)-like domain containing protein 1.Immunohistochemical analysis demonstrated that the SCUBE1 staining is mainly confined to the intravascular platelet-rich thrombus in vascular tissue samples. While quantitative real-time RT-PCR verified that the SCUBE1 mRNA is expressed in human platelets, numerous immunolocalization techniques revealed that the preformed SCUBE1 protein is stored in the alpha-granules and translocated to the surface upon platelet stimulation. A smaller SCUBE1 fragment, possibly formed by limited proteolysis after being released from the storage granules, was detected in thrombus lysate by Western blot analysis. Interestingly, deposition of SCUBE1 into the subendothelial matrix of the atherosclerotic plaques was evidenced by immunohistochemistry. In addition, studies of platelet adhesion and ristocetin-induced platelet agglutination showed that fragments containing the amino-terminal EGF-like repeats were able to support platelet adhesion and enhance the ristocetin-induced platelet agglutination, respectively.These data suggest that platelet-derived SCUBE1 could function as a novel adhesive molecule and its matrix-bound and soluble fragments may play critical (patho)physiological roles in cardiovascular biology.
Extent of regretted sexual intercourse among young teenagers in Scotland: a cross sectional survey
Authors: Daniel Wight, Marion Henderson, Gillian Raab, Charles Abraham, Katie Buston, Sue Scott, Graham Hart
Journal: BMJ (2000)

This cross sectional survey determined the extent of regretted sexual intercourse among young teenagers in Scotland. Using a questionnaire, data were obtained from 7395 third-year pupils (3365 boys and 3730 girls) aged 13 years and 6 months to 14 years and 9 months in 24 nondenominational state secondary schools. Regretted sexual intercourse, measured on a three-point scale, was analyzed by ordinal logistic regression. The data revealed that 18% (661) of boys and 15.4% (576) of girls had experienced sexual intercourse, of which 74.8% occurred since their 13th birthday. Boys, compared with girls, reported higher levels of regret. For boys, higher levels of regret were significantly associated with having exerted pressure to have sex. On multivariate analysis, reports of being pressured, exerting pressure, not having planned sexual intercourse with partner, and high levels of parental monitoring were significantly related to girls' regret. For women, regret seemed to be related to lack of control. Sex education should focus on assisting young people to develop relationship and negotiation skills. In addition, making teenagers aware of potential emotional and relationship consequences of early sexual intercourse may delay first intercourse.
Ebola and the wisdom of Haygarth
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2014)

Unusually, this issue of JRSM begins and ends with poetry. Salil Patel’s editorial on the role of instinct in medicine opens with a quote from Socrates which proposes poets write poetry on instinct rather than through wisdom.1 Instinct may not be backed by evidence. A judgement based on instinct may be unpopular. Medical journals tend to avoid poetry for these very reasons. One reader’s inspirational poem may be another’s nightmare verse. Nevertheless, two poems by poet Robert Vas Dias close this issue and describe his experience of transient ischaemic attacks.2 What are your instincts? Does poetry have a place in medical journals?

In 1793, reasoning, probably with a dash of instinct, led John Haygarth to propose his rules of prevention.3 Society was faced with a threat from an infectious disease that had no cure but a high death rate. Spread of the disease was fuelled by poverty and cramped living conditions. The USA approached smallpox with near panic. In Rhode Island, people with smallpox were sent to a ‘pest island’, transported in a large box with holes to admit air. The response in England may have been alarmist too but it was more measured, thanks largely to the work of Haygarth.

Smallpox was transmitted to a ‘susceptible individual by close contact or by contact with the clothes, scabs, or serum’. It was the Ebola of its day and Haygarth’s rules, now over 200 years old, may be equally applicable to the latest infectious disease to invoke mass fear. As a biographical piece by the late Christopher Booth explains, Haygarth’s rules ‘stressed that patients should be isolated, that no one who had not had the disease should enter the house of any victim, that no patient should be allowed out after the pocks had appeared, that the most utmost attention to cleanliness was absolutely essential, and that everything to do with the patient’s illness must be meticulously washed’.4

Haygarth’s rules worked for smallpox. He was ahead of his time though in proposing a grand plan for eradicating smallpox that was essentially a blueprint for our public health service. By contrast, the world’s response to Ebola is a throwback to the days when fear of disease dominated reason and even instinct. It is hard to find wisdom in our response to Ebola. There is plenty of politics and scaremongering. Would we allow the wisdom of a 21st Century Haygarth to be heard now? It seems unlikely. Perhaps as improbable as Socrates seeing wisdom in poets?
Mild Gestational Diabetes Mellitus and Long-Term Child Health
Authors: Mark B. Landon, Madeline Murguia Rice, Michael W. Varner, Brian M. Casey, Uma M. Reddy, Ronald J. Wapner, Dwight J. Rouse, Joseph R. Biggio, John M. Thorp, Edward K. Chien, George Saade, Alan M. Peaceman, Sean C. Blackwell, J. Peter VanDorsten
Journal: Diabetes Care (2014)

OBJECTIVE To evaluate whether treatment of mild gestational diabetes mellitus (GDM) confers sustained offspring health benefits, including a lower frequency of obesity. RESEARCH DESIGN AND METHODS Follow-up study of children (ages 5–10) of women enrolled in a multicenter trial of treatment versus no treatment of mild GDM. Height, weight, blood pressure, waist circumference, fasting glucose, fasting insulin, triglycerides, and HDL cholesterol were measured. RESULTS Five hundred of 905 eligible offspring (55%) were enrolled. Maternal baseline characteristics were similar between the follow-up treated and untreated groups. The frequencies of BMI ≥95th (20.8% and 22.9%) and 85th (32.6% and 38.6%) percentiles were not significantly different in treated versus untreated offspring (P = 0.69 and P = 0.26). No associations were observed for BMI z score, log waist circumference, log triglycerides, HDL cholesterol, blood pressure, or log HOMA-estimated insulin resistance (HOMA-IR). The effect of treatment was different by sex for fasting glucose and log HOMA-IR (P for interaction = 0.002 and 0.02, respectively) but not by age-group (5–6 and 7–10 years) for any outcomes. Female offspring of treated women had significantly lower fasting glucose levels. CONCLUSIONS Although treatment for mild GDM has been associated with neonatal benefits, no reduction in childhood obesity or metabolic dysfunction in the offspring of treated women was found. However, only female offspring of women treated for mild GDM had lower fasting glucose.
Intestinal fluid and electrolyte transport in human cholera
Authors: John G. Banwell, Nathaniel F. Pierce, Rupak C. Mitra, Kenneth L. Brigham, George J. Caranasos, Robert I. Keimowitz, David S. Fedson, Jacob Thomas, Sherwood L. Gorbach, R. Bradley Sack, Arabindo Mondal
Journal: Journal of Clinical Investigation (1970)

The site, nature, magnitude, and duration of fluid and electrolyte loss into the small intestine during the acute and recovery phase of human cholera was defined in 27 Indian patients. 11 subjects without cholera served as controls. The marker perfusion technique employed was shown, in preliminary experiments, to measure accurately jejunal and ileal fluid and electrolyte transmucosal transport rates under conditions of cholera diarrhea. Fluid loss into the lumen occurred from jejunal and ileal mucosa. The fluid was isotonic in both regions. Bicarbonate concentration was significantly higher in ileal than jejunal fluid during all phases of the disease. Bicarbonate concentration in both regions was significantly higher in acute cholera than during convalescence. Fluid loss into the intestinal lumen ranged from 0.07 to 10.9 ml/hr per cm. Losses were significantly greater from jejunum than ileum. Net ileal absorption was recorded in five of 10 acute cholera studies. During the acute phase of the disease, net jejunal fluid transport showed a positive correlation with fasting intestinal flow rate and stool output. Stool output was also positively correlated with jejunal fasting intestinal flow rates. Recovery of normal fluid and electrolyte absorptive function was usually complete in both jejunum and ileum by the sixth day after admission. These findings in human cholera validate the animal models of choleraic diarrhea and suggest that similar measurements of small intestinal secretory function in other nonspecific diarrheal diseases using the marker perfusion technique may be rewarding.
Promising Treatments for Women With Comorbid PTSD and Substance Use Disorders
Authors: Denise A. Hien, Lisa R. Cohen, Gloria M. Miele, Lisa Caren Litt, Carrie Capstick
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors' goal was to compare the efficacy of a manualized cognitive behavior therapy that addresses both posttraumatic stress disorder (PTSD) and substance abuse (seeking safety) with a manualized cognitive behavior therapy that addresses only substance abuse (relapse prevention) and with standard community care for the treatment of comorbid posttraumatic stress disorder (PTSD) and substance use disorder. METHOD: One hundred seven women from an urban, low-income population who had comorbid PTSD and substance use disorder were randomly assigned to receive the two kinds of cognitive behavior therapy or received standard community treatment. Participants were recruited from both community and clinical populations and evaluated with structured clinical instruments. Forty-one women received seeking safety therapy, 34 received relapse prevention therapy, and 32 received standard community care. RESULTS: At the end of 3 months of treatment, participants in both cognitive behavior therapy conditions had significant reductions in substance use, PTSD, and psychiatric symptoms, but community care participants worsened over time. Both groups receiving cognitive behavior therapy sustained greater improvement in substance use and PTSD symptoms at 6-month and 9-month follow-ups than subjects in the community care group. CONCLUSIONS: Seeking safety and relapse prevention are efficacious short-term treatments for low-income urban women with PTSD, substance use disorder, and other psychiatric symptoms.
Gold Foams for Drug Delivery: Microfabrication‐Compatible Nanoporous Gold Foams as Biomaterials for Drug Delivery (Adv. Healthcare Mater. 2/2012)
Authors: Erkin Seker, Yevgeny Berdichevsky, Kevin J. Staley, Martin L. Yarmush
Journal: Advanced Healthcare Materials (2012)

Nanoporous gold can be produced by a facile self-assembly process that is compatible with conventional microfabrication techniques. On page 172, Erkin Seker and co-workers demonstrate this material's biocom-patibility and its capability to deliver drugs for modulating cellular response. The cover image, acquired with a high-resolution scanning electron microscope, illustrates an astrocyte latching onto the grooves of a nanoporous gold surface.
THE RADIUM TREATMENT OF GENITOURINARY CANCER
Authors: A. C. Morson
Journal: BMJ (1930)

TMEIcABRJiouBNA 953 3.In cases of early iinfiltrating carcinoma, whether papilli- ferous or ulcerating, conifinied to one side of the bladder, I shall retuirn to my originial practice, which I have employed since 91l0-namely, 'wide extraperitoneal resection of the l)ladder wall withi reaction and re-implantation of one or even both ureters.Into the fresh wouind so nmade I slhall hesitate to implanit radoni seeds, as I fear that these will delay or prevent proper liealing.Experience has tauight me that the
Molecular mechanisms for telomere maintenance in neuroblastoma.
Authors: Armita Bahrami, Seungjae Lee, Yiping Fan, John Morris, Alberto S. Pappo, Wayne Lee Furman
Journal: Journal of Clinical Oncology (2015)

10041 Background: Despite a well-developed risk classification schema utilizing both clinical and biologic factors, the clinical outcome of neuroblastoma (NB) is remarkably heterogeneous. Replicative immortality in cancers is mediated by 2 known telomere maintenance mechanisms (TMMs): telomerase reactivation and alternative lengthening of telomere (ALT). We hypothesized that TMMs are essential for cancer development in high-risk NBs (HR-NBs) but not low-risk or stage 4S NBs that frequently undergo spontaneous regression. We investigated the prevalence of known molecular events involved in TMMs in NB risk categories. Methods: The analysis included 47 NBs from 27 patients with high-risk disease and poor outcomes and 19 patients with low- or intermediate-risk disease and good outcomes (LR-NBs). Presence of the ALT phenotype was determined by telomeric fluorescence in situ hybridization (FISH), and its association with ATRX alterations was evaluated by immunohistochemistry. Direct sequencing of the TERT promoter (TERT-p) to screen for hotspot mutations and TERT copy number FISH to assess gene amplification were conducted. For methylation analysis, 500 ng of bisulfite-converted DNA was processed and hybridized on the Illumina HumanMethylation450 BeadChip. RNA in situ hybridization (ISH) for TERT was performed on 4 HR-NBs to observe TERT expression. Results: Methylation analysis showed that TERT-p CpGs at positions ch5:1295737 and 1295799 were the most differentially methylated regions between HR-NBs and LR-NBs (P< 0.0005). Of the 27 HR-NBs, 11 (41%) were hypermethylated in one or both CpG regions; 7 (26%) exhibited an ALT phenotype, of which 5 were associated with heterogeneous or loss of ATRX expression; 3 had TERT amplification; 2 carried a TERT-p mutation; and 5 (19%) showed no alterations. In contrast, the assays were negative in all 19 LR-NBs. RNA ISH for TERT showed high-resolution signals in TERT-p methylated but no signals in ALT-phenotype HR-NBs. Conclusions: Molecular mechanisms for telomere maintenance in HR-NB are diverse and commonly associated with hypermethylation of the TERT-p region. Future studies to assess the prognostic relevance of these biomarkers on clinical outcomes in patients with NB are warranted.
Generation of unique mono-hydroxy-eicosatetraenoic acids from arachidonic acid by human neutrophils.
Authors: E J Goetzl, F F Sun
Journal: The Journal of Experimental Medicine (1979)

Incubation of [3H]arachidonic acid with the 17,000-g supernatant from homogenates of human neutrophils in the presence of indomethacin generated the unique metabolites 9-OH-5,7,11,14-eicosatetraenoic acid (9-HETE) and 8-HETE, in addition to 12-HETE, 11-HETE and 5-HETE. The human neutrophil chemotactic activity of the HETE products exhibited a rank-order of potency with 5-HETE greater than 8-HETE = 9-HETE greater than 11-HETE = 12-HETE. The expression of chemokinetic activity as well as chemotactic activity suggested that the endogenous production of these principles may influence the mobility of human neutrophils.
Blood tests in the management of Helicobacter pylori infection
Authors: D Vaira, J Holton, M Menegatti, F Landi, C Ricci, A Ali', L Gatta, S Farinelli, C Acciardi, B Massardi, M Miglioli
Journal: Gut (1998)

There are three main types of blood test available for the management of Helicobacter pylori infection: those that detect an antibody response; tests of the pathophysiological state of the stomach; and those that indicate an active infection.Enzyme linked immunosorbent assay (ELISA) based kits are the most numerous of the commercially available tests.Originally the kits used crude antigen preparations but many of the newer kits use a more purified antigen preparation giving increased specificity but a lower sensitivity.The sensitivity, specificity, and predictive values of the tests can also be aVected by the population under test and coexistent disease in the patients.Near patient test kits are based on either latex agglutination or immunochromatography. Generally, they have low sensitivities compared with laboratory tests.Commerical western blotting kits have also been developed and are used to detect the presence of specific virulence markers.The exact role of serology in the management of Helicobacter infection has still to be defined, although there is evidence that, used as a screening procedure, it can reduce endoscopy cost and workload.Gastrin and pepsinogen blood concentrations may provide valuable information on the pathophysiological state of the stomach-for example, the presence of inflammation or gastric atrophy.A combination of serology and serum concentrations of gastrin and pepsinogen may be used effectively to detect serious gastroduodenal disease in patients.
Dihydropteridine reductase deficiency in man: From biology to treatment
Authors: Alberto Ponzone, Marco Spada, Silvio Ferraris, Irma Dianzani, Luisa de Sanctis
Journal: Medicinal Research Reviews (2003)

Abstract In 1975, dihydropteridine reductase (DHPR) deficiency was first recognized as a cause of tetrahydrobiopterin (BH 4 ) deficiency, leading to hyperphenylalaninemia (HPA) and impaired biogenic amine deficiency. So far, more than 150 patients scattered worldwide have been reported and major progresses have been made in the understanding of physiopathology, screening, diagnosis, treatment, and molecular genetics of this inherited disease. Present knowledge on different aspects of DHPR deficiency, largely derived from authors' personal experience, is traced in this article. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 2, 127–150, 2004
Targeting Hyaluronidase for Cancer Therapy: Antitumor Activity of Sulfated Hyaluronic Acid in Prostate Cancer Cells
Authors: Anaid Benitez, Travis J. Yates, Luis E. Lopez, Wolfgang H. Cerwinka, Ashraf Bakkar, Vinata B. Lokeshwar
Journal: Cancer Research (2011)

Abstract The tumor cell–derived hyaluronidase (HAase) HYAL-1 degrades hyaluronic acid (HA) into proangiogenic fragments that support tumor progression. Although HYAL-1 is a critical determinant of tumor progression and a marker for cancer diagnosis and metastasis prediction, it has not been evaluated as a target for cancer therapy. Similarly, sulfated hyaluronic acid (sHA) has not been evaluated for biological activity, although it is an HAase inhibitor. In this study, we show that sHA is a potent inhibitor of prostate cancer. sHA blocked the proliferation, motility, and invasion of LNCaP, LNCaP-AI, DU145, and LAPC-4 prostate cancer cells, and induced caspase-8–dependent apoptosis associated with downregulation of Bcl-2 and phospho-Bad. sHA inhibited Akt signaling including androgen receptor (AR) phosphorylation, AR activity, nuclear factor κB (NFκB) activation, and VEGF expression. These effects were traced to a blockade in complex formation between phosphoinositide 3-kinase (PI3K) and HA receptors and to a transcriptional downregulation of HA receptors, CD44, and RHAMM, along with PI3K inhibition. Angiogenic HA fragments or overexpression of myristoylated Akt or HA receptors blunted these effects of sHA, implicating a feedback loop between HA receptors and PI3K/Akt signaling in the mechanism of action. In an animal model, sHA strongly inhibited LNCaP-AI prostate tumor growth without causing weight loss or apparent serum-organ toxicity. Inhibition of tumor growth was accompanied by a significant decrease in tumor angiogenesis and an increase in apoptosis index. Taken together, our findings offer mechanistic insights into the tumor-associated HA–HAase system and a preclinical proof-of-concept of the safety and efficacy of sHA to control prostate cancer growth and progression. Cancer Res; 71(12); 4085–95. ©2011 AACR.
The limitations of the "Stanford 25"
Authors: T. Nicholson
Journal: BMJ (2010)

<h3>Abstract</h3> Despite being a weak point in their life cycle, transmission of <i>Plasmodium</i> parasites from humans to mosquitoes is an understudied field of research. Direct membrane feeding assays (DMFA) are an important tool, allowing detailed mechanistic malaria transmission studies from humans to mosquitoes. Especially for <i>Plasmodium vivax</i>, which cannot be cultured long-term under laboratory conditions, implementation of DMFAs requires proximity to <i>P. vivax</i> endemic areas. In the present study, we investigated the infectivity of symptomatic <i>Plasmodium</i> infections to <i>Anopheles farauti</i> colony mosquitoes in Papua New Guinea (PNG), a country with one of the highest rates of <i>Plasmodium vivax</i> in the world. A total of 182 DMFAs were performed with venous blood collected from symptomatic malaria patients positive by rapid diagnostic test (RDT). DMFAs resulted in mosquito infection in 20.9% (38/182) of cases. The parasite species in the blood feeds were determined retrospectively by expert light microscopy and quantitative real-time qPCR. Based on light microscopy, 9.2% of <i>P. falciparum</i> and 42% of <i>P. vivax</i> human infections resulted in mosquito infections. Infections containing gametocytes detected by microscopy led to mosquito infections in 58.8% of <i>P. vivax</i> and 8.7% of <i>P. falciparum</i> infections. Based on qPCR, 10% of <i>P. falciparum</i> and 43.6% of <i>P. vivax</i> lead to a successful mosquito infection. Venous blood samples from symptomatic <i>P. vivax</i> patients were more infectious to <i>An. farauti</i> mosquitoes in DMFAs compared to <i>P. falciparum</i> infected patients. The capacity to perform DMFAs in a high-burden <i>P. vivax</i> setting creates a unique opportunity to address critical gaps in our understanding of <i>P. vivax</i> human-tomosquito transmission.
Granular lymphocyte leukemia with pure red cell aplasia: Usefulness of gene analysis in assessing therapeutic effect
Authors: Toshiko Motoji, Osamu Yamada, Masatomo Takahashi, Kazuo Oshimi, Hideaki Mizoguchi
Journal: American Journal of Hematology (1992)

Abstract A patient with granular lymphocyte leukemia (GLL) of the CD3 + , CD4 ‐ , CD8 + phenotype accompanied by pure red cell aplasia (PRCA) is described. Surface marker analysis, nonmajor histocompatibility complex (MHC)‐restricted cytotoxicity assay, gene analysis, and in vitro colony assay were performed on the granular lymphocytes before and after treatment. Cyclophospharnide therapy was highly effective, and after remission clonal granular lymphocytes were no longer identified by T‐cell antigen receptor (TCR) gene analysis or surface marker analysis. Lymphocytes obtained after remission did not exhibit elevated levels of non‐MHC‐restricted cytotoxicity, nor did they demonstrate a suppressive effect on erythroid colony formation. TCR gene analysis proved to be a sensitive parameter for evaluating the residual malignant granular lymphocytes. Gene analysis will be useful both for timing the discontinuation of treatment and for the early detection of relapse. Various factors possibly related to the development of PRCA in this patient were investigated and their significance is discussed.