tbuckley/cabot-search huggingface dataset:
Clinical and Molecular Genetic Spectrum of Congenital Deficiency of the Leptin Receptor
Authors: I. Sadaf Farooqi, Teresia Wangensteen, Stephan Collins, Wendy Kimber, Giuseppe Matarese, Julia M. Keogh, Emma Lank, Bill Bottomley, Judith Lopez-Fernandez, Ivan Ferraz-Amaro, Mehul T. Dattani, Oya Ercan, Anne Grethe Myhre, Lars Retterstol, Richard Stanhope, Julie A. Edge, Sheila McKenzie, Nader Lessan, Maryam Ghodsi, Veronica De Rosa, Francesco Perna, Silvia Fontana, Inês Barroso, Dag E. Undlien, Stephen O'Rahilly
Journal: New England Journal of Medicine (2007)

A single family has been described in which obesity results from a mutation in the leptin-receptor gene (LEPR), but the prevalence of such mutations in severe, early-onset obesity has not been systematically examined.We sequenced LEPR in 300 subjects with hyperphagia and severe early-onset obesity, including 90 probands from consanguineous families, and investigated the extent to which mutations cosegregated with obesity and affected receptor function. We evaluated metabolic, endocrine, and immune function in probands and affected relatives.Of the 300 subjects, 8 (3%) had nonsense or missense LEPR mutations--7 were homozygotes, and 1 was a compound heterozygote. All missense mutations resulted in impaired receptor signaling. Affected subjects were characterized by hyperphagia, severe obesity, alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism. Serum leptin levels were within the range predicted by the elevated fat mass in these subjects. Their clinical features were less severe than those of subjects with congenital leptin deficiency.The prevalence of pathogenic LEPR mutations in a cohort of subjects with severe, early-onset obesity was 3%. Circulating levels of leptin were not disproportionately elevated, suggesting that serum leptin cannot be used as a marker for leptin-receptor deficiency. Congenital leptin-receptor deficiency should be considered in the differential diagnosis in any child with hyperphagia and severe obesity in the absence of developmental delay or dysmorphism.
10265-84 Impact of the Defibrillating Surface Area of an Additional Superior Vena Cava Electrode on the Unipolar Right Ventricular Coil/Defibrillator Can System
Authors: Keith Newby, Lynn Moredock, Judy Rembert, J. Marcus Wharton, Robert Sorrentino, Ruth Ann Greenfield, Kenneth G. Morris, Andrea Natale
Journal: Journal of the American College of Cardiology (1995)
PROSTATECTOMY VERSUS PROSTATOTOMY IN THE RADICAL TREATMENT OF SENILE HYPERTROPHY OF THE PROSTATE.
Authors: RAMON GUITERAS
Journal: JAMA (1901)

In senile hypertrophy of the prostate there is sometimes obstruction to the outflow of urine, due to an enlargement or deformity of the middle or lateral lobes, giving rise to a series of disagreeable symptoms, such as frequency of urination, pain, tenesmus, burning or acute retention, and resulting in complete or incomplete retention, followed in nearly every case by cystitis, pyelitis, and fatal nephritis or pyelonephritis. With the object of overcoming this condition the following various procedures have been resorted to: The use of the catheter to relieve the retention by drawing off the urine as frequently as indicated by the amount of residuum; suprapubic fistula, by means of which an artificial urethra is made in the hypogastric region, through which the patient urinates, or draws his urine by a catheter or tube; dilatation of the prostatic urethra with sounds or dilators every few days; galvano-puncture, by means of a
Nonsyndromic paucity of intrahepatic bile ducts in infancy and idiopathic ductopenia in adulthood: The same syndrome?
Authors: Miquel Bruguera, Josep Llach, Joan Rodés
Journal: Hepatology (1992)

Eleven patients with chronic intrahepatic cholestasis in whom a liver biopsy specimen showed unexplained bile duct paucity were investigated. Cholestasis developed during the neonatal period in three, at infancy (before 14 yr) in four and after 14 yr in the remaining four patients. In all patients other conditions characterized by chronic cholestasis associated with ductopenia such as primary biliary cirrhosis, primary sclerosing cholangitis, drug-induced liver disease, sarcoidosis or graft-vs.-host disease were excluded. Cardiovascular abnormalities in the three patients who had neonatal cholestasis permitted diagnosis of Alagille's syndrome. Clinical, biochemical and histological features were similar in the remaining eight patients, independent of the age at which the disease appeared. Idiopathic adulthood ductopenia may be a late-onset form of the nonsyndromic paucity of interlobular bile ducts seen in children, or it may be due to a still-unidentified cause that strikes later in life. (HEPATOLOGY 1992;15:830–834).
Consultants' Views of General Practitioners
Authors: N. Cash
Journal: BMJ (1967)

on-coming cars would be cut out, since there would be a 90' rotation.Awareness of on- coming traffic may be achieved by using a Polaroid material of suitable density and efficiency so that not all light is stopped.Fog light would be exempt.If headlight adaptation is made compulsory it leaves the choice of selecting the method of cut-out to the individual driver, should he so desire.Th. most convenient but expensive way would be by incorporating the material between the layers of the windscreen during manufacture, but the alternatives mentioned above would be simpler and cheaper.Head- lights may be adapted by using clip-on polaroid screens or by inserting them on the inside of the glass during assembly.-Iam, etc.,
New scoring system predicts cardiovascular disease risk worldwide
Authors: S. Mayor
Journal: BMJ (2015)

Researchers have developed the first risk scoring system that can be used to predict cardiovascular disease (CVD) risk in people worldwide. It estimates that a higher percentage of people are at high risk of fatal CVD in low and middle income countries than in higher income countries.1

Treatment of cardiovascular risk factors depends on having valid risk prediction equations, but these have previously been developed and validated for …
Dominantly transmitted hematologic dysfunction clinically similar to fanconi's anemia
Authors: Carol L. Alter, Paul H. Levine, John Bennett, Craig Kessler, Margaret Rick, Ronald G. Washburn, John I. Gallin, Robert W. Miller, Arleen D. Auerbach
Journal: American Journal of Hematology (1989)

Abstract We report a family with a dominantly transmitted syndrome resembling Fanconi's anemia and spanning two generations. This syndrome was characterized by an ill‐defined hematologic stem cell disorder, immune dysfunction, poor dentition, hyperpigmented skin, warts, and multiple second trimester spontaneous abortions and included one case of acute myelomonocytic leukemia (acute non‐lymphocytic leukemia, M4). This family lacks the characteristic chromosomal aberrations of Fanconi's anemia. We believe this constellation of findings represents an entity not previously described.
Delivery of Ricin Toxin A‐Chain by Peptide‐Targeted Mesoporous Silica Nanoparticle‐Supported Lipid Bilayers
Authors: Katharine Epler, David Padilla, Genevieve Phillips, Peter Crowder, Robert Castillo, Dan Wilkinson, Brian Wilkinson, Cameron Burgard, Robin Kalinich, Jason Townson, Bryce Chackerian, Cheryl Willman, David Peabody, Walker Wharton, C. Jeffrey Brinker, Carlee Ashley, Eric Carnes
Journal: Advanced Healthcare Materials (2012)

Mesoporous silica nanoparticle-supported lipid bilayers, or "protocells", exhibit a high loading capacity, enhanced colloidal stability, and peptide-directed, cell-specific uptake, making them especially well-suited for targeted delivery of protein toxins to cancer. Protocells loaded with ricin toxin A-chain (RTA) and targeted to hepatocellular carcinoma cause complete cell death at 30 pM of RTA without affecting the viability of control hepatocytes.
Prognostic Role of<i>E2F1</i>and Members of the<i>CDKN2A</i>Network in Gastrointestinal Stromal Tumors
Authors: Florian Haller, Bastian Gunawan, Anja von Heydebreck, Stefanie Schwager, Hans-Jürgen Schulten, Judith Wolf-Salgó, Claus Langer, Giuliano Ramadori, Holger Sültmann, László Füzesi
Journal: Clinical Cancer Research (2005)

The aim of the current study was to examine the prognostic relevance of the CDKN2A tumor suppressor pathway in gastrointestinal stromal tumors (GIST).We determined the mRNA expression of p1(INK4A), p14(ARF), CDK4, RB1, MDM2, TP53, and E2F1 by quantitative reverse transcription-PCR in 38 cases of GISTs and correlated the findings with clinicopathologic factors, including mutation analysis of KIT and PDGFRA.The k-means cluster analysis yielded three prognostic subgroups of GISTs with distinct mRNA expression patterns of the CDKN2A pathway. GISTs with low mRNA expression of the CDKN2A transcripts p16(INK4A) and p14(ARF) but high mRNA expression of CDK4, RB1, MDM2, TP53, and E2F1 were associated with aggressive clinical behavior and unfavorable prognosis, whereas GISTs with a low mRNA expression of CDK4, RB1, MDM2, TP53, and E2F1 were not. GISTs with a moderate to high mRNA expression of all examined genes also seemed to be associated with unfavorable prognosis. Regarding mutation analysis, we found significant differences in the KIT/PDGFRA genotype among the three clusters. Univariate analysis revealed high expression of E2F1 to be associated with mitotic count, proliferation rate, KIT mutation, and aggressive clinical behavior. These findings on mRNA level could be confirmed by immunohistochemistry.Our findings implicate differential regulation schemes of the CDKN2A tumor suppressor pathway converging to up-regulation of E2F1 as the critical link to increased cell proliferation and adverse prognosis of GISTs.
Argon Plasma Coagulation for the Treatment of Colonic Varices
Authors: T. W. Schafer, K. F. Binmoeller
Journal: Endoscopy (2002)

Various individually tailored endoscopic treatment modalities have been described for bleeding colorectal varices. We describe a case of a 65-year-old man, in whom argon plasma coagulation successfully eradicated ectopic varices at the ileocolonic anastomosis; bleeding could be stopped.
Suicide in Different Cultures
Authors: L. D. Hankoff
Journal: JAMA (1976)

Each of the 17 papers takes a specific cultural, ethnic, or national group as its focus; and the reader finds a balance of statistical and descriptive features of suicide around the world. The wide representation of individual nations, however, reflects the voluntary participants at the conference (no papers pertaining to Africa, the Soviet Union, or the People's Republic of China are present). The work of Durkheim and his intellectual forebears made abundantly clear that cultural factors are significant in the pattern of suicide throughout the world. Suicidology is by no means a new field nor are the efforts at prevention any longer in the incipient phase. For example, Atkinson noted that every major town in Britain has a telephone emergency service for the suicidal individual who wants to communicate and receive some form of help. In general, however, the problem of the prevention of suicide has remained an elusive one,
Chemistry and Treatment of Adrenocortical Diseases
Authors: Don H. Nelson
Journal: JAMA (1964)

This is a well-written description of the chemistry of adrenocortical disease. The author has had considerable experience in the investigation of adrenocortical disturbances which is well reflected in the volume. Although somewhat technical for the average practitioner, it is written with sufficient clarity to make the chemistry understandable to most physicians who are willing to spend some time with it. The volume should be particularly well suited to the individual who would like to know more than is found in the standard textbooks of medicine or even general endocrinologic texts. This book is remarkably current, and the author is to be complimented for his successful integration of many isolated investigations into a very readable description of an active research area. It is rare to avoid errors completely and thus Fig 2 mistakenly shows angular methyl groups in the 19 position of the estrogens but this is not repeated in Fig
Litholapaxy: 385 Cases
Authors: R. Brito, H. Borges, j. Albuquerque, R. Zulian
Journal: Endoscopy (1975)

The authors present the results of 385 litholapaxies done over a period of twenty seven and a half years. The blind litholapaxy technique used in 98.44% of the cases is reviewed. No serious complications were noted in patients submitted to this procedure alone.
HYPOTENSIVE EFFECTS OF IPRONIAZID AND CARBOXAZID
Authors: Nicholas S. Assali
Journal: JAMA (1960)

The authors have investigated the hemodynamic changes accompanying the hypotension that occasionally follows administration of amine oxidase inhibitors, particularly iproniazid phosphate. Iproniazid was given intravenously and orally, in varying doses, to hospitalized patients with toxemia of pregnancy or with essential hypertension associated with pregnancy. Similar observations were made with carboxazid, an analogue of iproniazid. Data on blood pressure in supine and upright positions and on renal hemodynamics and cardiac output indicated that the hypotension was probably caused by venous pooling and by a decrease in the cardiac output rather than by a true vasodilator action.
Fluorescence Imaging in Surgery
Authors: Ryan K. Orosco, Roger Y. Tsien, Quyen T. Nguyen
Journal: IEEE Reviews in Biomedical Engineering (2013)

Although the modern surgical era is highlighted by multiple technological advances and innovations, one area that has remained constant is the dependence of the surgeon's vision on white-light reflectance. This renders different body tissues in a limited palette of various shades of pink and red, thereby limiting the visual contrast available to the operating surgeon. Healthy tissue, anatomic variations, and diseased states are seen as slight discolorations relative to each other and differences are inherently limited in dynamic range. In the upcoming years, surgery will undergo a paradigm shift with the use of targeted fluorescence imaging probes aimed at augmenting the surgical armamentarium by expanding the "visible" spectrum available to surgeons. Such fluorescent "smart probes" will provide real-time, intraoperative, pseudo-color, high-contrast delineation of both normal and pathologic tissues. Fluorescent surgical molecular guidance promises another major leap forward to improve patient safety and clinical outcomes, and to reduce overall healthcare costs. This review provides an overview of current and future surgical applications of fluorescence imaging in diseased and nondiseased tissues and focus on the innovative fields of image processing and instrumentation.
The clinical utility of the dexamethasone suppression test in psychiatry. Summary of a National Institute of Mental Health workshop
Authors: Robert M. A. Hirschfeld, Stephen H. Koslow, David J. Kupfer
Journal: JAMA (1983)

The dexamethasone suppression test (DST) is being increasingly used in psychiatry, especially in the differential diagnosis of affective disorders. In light of this, the National Institute of Mental Health convened a workshop of clinical scientists drawn from neuroendocrinology, psychopathology, and general clinical psychiatry to review the evidence for the efficacy of the use of the DST in psychiatry. Specifically considered were DST's relevance to differential diagnosis, its use as a predictor of response to treatment, its relationship with other biologic variables, and technical issues. The panelists concluded that at this time there are no clear indications for routine use of the DST in diagnosis or clinical management of depression, although it is a useful research tool. Areas of potential utility include prediction of suicidal activity, prediction of relapse, and differential diagnosis.
Critical Roles for Polymerase ζ in Cellular Tolerance to Nitric Oxide–Induced DNA Damage
Authors: Xiaohua Wu, Katsuya Takenaka, Eiichiro Sonoda, Helfrid Hochegger, Shosuke Kawanishi, Takuo Kawamoto, Shunichi Takeda, Mitsuyoshi Yamazoe
Journal: Cancer Research (2006)

Nitric oxide (NO), a signal transmitter involved in inflammation and regulation of smooth muscle and neurons, seems to cause mutagenesis, but its mechanisms have remained elusive. To gain an insight into NO-induced genotoxicity, we analyzed the effect of NO on a panel of chicken DT40 clones deficient in DNA repair pathways, including base and nucleotide excision repair, double-strand break repair, and translesion DNA synthesis (TLS). Our results show that cells deficient in Rev1 and Rev3, a subunit essential for DNA polymerase zeta (Polzeta), are hypersensitive to killing by two chemical NO donors, spermine NONOate and S-nitroso-N-acetyl-penicillamine. Mitotic chromosomal analysis indicates that the hypersensitivity is caused by a significant increase in the level of induced chromosomal breaks. The data reveal the critical role of TLS polymerases in cellular tolerance to NO-induced DNA damage and suggest the contribution of these error-prone polymerases to accumulation of single base substitutions.
Strategies for an HIV vaccine
Authors: Norman L. Letvin
Journal: Journal of Clinical Investigation (2002)

The future of vaccine designThe development of an HIV vaccine poses an unprecedented challenge to the scientific community.The inexorable spread of HIV worldwide and the devastating clinical consequences of AIDS can only be contained by an effective vaccine.Yet, almost two decades after the first demonstration of HIV and its etiologic role in AIDS, this vaccine still is a goal, not a reality.In this Perspective, I consider the unique problems for vaccine development posed by the biology of HIV infection, and I summarize recent advances in our understanding of the immune control of HIV and the implications of these advances for vaccine development.After reviewing the sobering history of failed traditional vaccine strategies, I discuss the rationale for vaccines with novel designs and their experimental successes to date. AIDS animal modelsAppropriate animal models have been key to the elucidation of AIDS immunopathogenesis and the assessment of HIV vaccine strategies.Nonhuman primates represent a particularly powerful model for the study of AIDS.The HIV-1 and HIV-2 isolates that infect humans are members of a large family of lentiviruses that endemically infect nonhuman primate species of Africa.These nonhuman primate viruses are known as simian immunodeficiency viruses (SIVs).Interestingly, they cause no disease in their natural host species.However, some of these isolates cause AIDS when inoculated experimentally in Asian macaques (2).Moreover, chimeric viruses have been developed that Strategies for an HIV vaccine
The use of higher dose clofarabine in adults with relapsed acute lymphoblastic leukemia
Authors: Bradley A. McGregor, Alexander W. Brown, Michael B. Osswald, Michael R. Savona
Journal: American Journal of Hematology (2009)

Abstract The standard dose of clofarabine is 52 mg/m 2 for pediatrics and 40 mg/m 2 in adults. Clofarabine dosed at 52 mg/m 2 was used in adult patients with refractory ALL to maximize response before allo‐HSCT. All patients had a significant response to therapy. Published pharmacokinetic analysis revealed no difference in peak plasma or intracellular concentrations at clofarabine dosed above 40 mg/m 2 , yet inhibition of replication in leukemia cells was only sustained over 24 hr at 55 mg/m 2 . Despite this, there have been no reports of high dose clofarabine used in this setting. Our experience implies that there may be a niche role for clofarabine in reducing disease burden before allo‐HSCT for adults with relapsed ALL. Am. J. Hematol., 2009. Published 2009 Wiley‐Liss, Inc.
AUGMENTATION OF IN-VITRO HIV REPLICATION IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF AIDS AND ARC PATIENTS BY TUMOUR NECROSIS FACTOR
Authors: Suzuki Michihiko, Naoki Yamamoto, Fumihiko Shinozaki, Kaoru Shimada, Gen-Ichiro Soma, Nobuyuki Kobayashi
Journal: The Lancet (1989)
Tobacco company makes freedom of information request for university's research
Authors: B. Christie
Journal: BMJ (2011)

A Scottish university may be forced to hand over detailed research into teenage smoking to a cigarette manufacturer after failing to block a request it made under freedom of information legislation.

Gerard Hastings, director of the Centre for Tobacco Control at the University of Stirling, said that such an outcome would be “catastrophic” and would have enormous implications for academic freedom.

Philip Morris International, one of the world’s largest tobacco companies, has submitted a series of freedom of information requests to get access to the Stirling centre’s research into the smoking behaviour of British teenagers.

The university has resisted the requests, …
Effect of calcium deposition on copper IUDs.
Authors: J Guillebad
Journal: BMJ (1977)

<b>Introduction:</b> The Department of Health document <i>Reforming emergency care</i> stated that new initiatives need to be developed to improve the care and assessment of patients. The Audit Commission has suggested that ambulance services should be allowed to decide who should be sent to each type of emergency and treat some patients at home. <b>Aims:</b> This scheme explores a new way of providing clinical assessment of older patients in their homes or in care homes within Sheffield. It sets out to provide a very patient centred model of care by providing community based clinical assessment for patients presenting to the emergency services with minor acute conditions. <b>Scope, development, and structure of scheme:</b> The scheme trains paramedic practitioners in the assessment and treatment of minor conditions to emergency nurse practitioner level. It consists of a three week full time theory based course and a 45 day period of supervised clinical practice based in the emergency department, minor injury unit, care of the elderly falls clinic, and with community services. Subsequently, the competence of the practitioners is assessed. <b>Service delivery:</b> The service will be activated by a 999 call between 0800 to 2000 each day. It is anticipated that between 25% to 50% of patients eligible to receive the service will be assessed and treated within the home. This approach to providing emergency care is untested and the frequency of use, patient acceptability, safety, and cost effectiveness are unknown, therefore rigorous assessment is essential through a randomised controlled trial.
Interleukin 6 is autoregulated by transcriptional mechanisms in cultures of rat osteoblastic cells.
Authors: N Franchimont, S Rydziel, E Canalis
Journal: Journal of Clinical Investigation (1997)

Interleukin 6 (IL-6), a cytokine produced by skeletal cells, stimulates osteoclast recruitment. The IL-6 soluble receptor (sIL-6R) increases IL-6 activity, and IL-6 and sIL-6R levels are increased in conditions of increased bone resorption. We examined the production of IL-6 by primary rat osteoblasts (Ob cells) cultured in the presence of IL-6 and sIL-6R. IL-6 alone did not induce IL-6 transcripts, but IL-6 was stimulatory in the presence of sIL-6R. Furthermore, sIL-6R by itself increased IL-6 transcripts. Cycloheximide superinduced IL-6 transcripts and did not prevent the effect of IL-6 and sIL-6R. IL-6 in the presence of sIL-6R stimulated IL-6 rates of transcription and the activity of IL-6 promoter fragments in transiently transfected Ob cells. 5' deletions of the IL-6 promoter and targeted mutations of the multiple response element (MRE)/cAMP responsive element (CRE), the nuclear factor for IL-6 (NF-IL-6), and the nuclear factor-kappaB (NF-kappaB) binding sites indicated that NF-IL-6 and NF-kappaB, in combination with MRE/CRE, binding sites are required for the induction of the IL-6 promoter by IL-6. In conclusion, IL-6 induces its own synthesis in osteoblasts by transcriptional mechanisms. This positive feedback may be important in conditions of increased bone resorption.