tbuckley/cabot-search huggingface dataset:
Lower CSF Amyloid Beta Peptides and Higher F2-Isoprostanes in Cognitively Intact Elderly Individuals With Major Depressive Disorder
Authors: Nunzio Pomara, Davide Bruno, Antero S. Sarreal, Raymundo T. Hernando, Jay Nierenberg, Eva Petkova, John J. Sidtis, Thomas M. Wisniewski, Pankaj D. Mehta, Domenico Pratico, Henrik Zetterberg, Kaj Blennow
Journal: American Journal of Psychiatry (2012)

Objective: Major depressive disorder is common in the elderly, and symptoms are often not responsive to conventional antidepressant treatment, especially in the long term. Soluble oligomeric and aggregated forms of amyloid beta peptides, especially amyloid beta 42, impair neuronal and synaptic function. Amyloid beta 42 is the main component of plaques and is implicated in Alzheimer's disease. Amyloid beta peptides also induce a depressive state in rodents and disrupt major neurotransmitter systems linked to depression. The authors assessed whether major depression was associated with CSF levels of amyloid beta, tau protein, and F2-isoprostanes in elderly individuals with major depressive disorder and age-matched nondepressed comparison subjects. Method: CSF was obtained from 47 cognitively intact volunteers (major depression group, N=28; comparison group, N=19) and analyzed for levels of soluble amyloid beta, total and phosphorylated tau proteins, and isoprostanes. Results: Amyloid beta 42 levels were significantly lower in the major depression group relative to the comparison group, and amyloid beta 40 levels were lower but only approaching statistical significance. In contrast, isoprostane levels were higher in the major depression group. No differences were observed in total and phosphorylated tau proteins across conditions. Antidepressant use was not associated with differences in amyloid beta 42 levels. Conclusions: Reduction in CSF levels of amyloid beta 42 may be related to increased brain amyloid beta plaques or decreased soluble amyloid beta production in elderly individuals with major depression relative to nondepressed comparison subjects. These results may have implications for our understanding of the pathophysiology of major depression and for the development of treatment strategies.
62 The use of NS5 protein-transduced dendritic cells as a novel approach for vaccination against hepatitis C virus
Authors: N KUZUSHITA, S GEHRING, S GREGORY, J WANDS
Journal: Hepatology (2003)

A set of 150 synthetic peptides spanning the proteins NS3-NS4-NS5 of the hepatitis C virus (HCV) was synthesizedand tested with a panel of 20 sera obtained from HCV-infected patients. Of 62 peptides prepared from the NS3 region, none exhibited strong antigenic reactivity. Rather, five peptides from this region demonstrated specific reactivity with only 5–10% of anti-HCV-positive sera. Nonetheless, it is well known that the NS3 region contains strong antigenic epitopes. These epitopes appear to be modeled in a functionally active manner with recombinant proteins and cannot be mimicked properly with short synthetic peptides. This finding suggests that the major NS3 antigenic epitopes are conformationally dependent. Seven of 20 peptides prepared from the NS4 region were immunoreactive. Five peptides from this region demonstrated very strong HCV-specific antigenic reactivity. Four of the five peptides belong to the recognized immunoreactive 5-1-1 region located inside the C100-3 antigen. One peptide demonstrating immunoreactivity with approximately 90% of anti-HCV-positive sera was found outside the C100-3 region at the C-terminal part of the NS4 protein. Of 68 peptides synthesized from the NS5 protein, 30 were immunoreactive. Six of the 30 demonstrated immunoreactivity with 35–50% of anti-HCV-positive sera. Thus, the NS4 and NS5 regions of the HCV polyprotein contain a large number of specific, broadly reactive, linear antigenic epitopes. The highly antigenic reactivity of the NS5 region suggests that this protein may have significant diagnostic potential.
How Much Will Health Care Reform Cost?
Authors: Marcia Angell
Journal: New England Journal of Medicine (1993)

Much of the current apprehension about health care reform stems from the assumption that a universal and comprehensive health care system would necessarily cost more than we are now spending. The assumption is reasonable; after all, we would be expanding coverage, and you can't get something for nothing. But this view presumes that we are now getting our money's worth. I will here argue that this is far from the case -- that, on the contrary, we are now spending so much on health care that we could cover all medically indicated care for all Americans without any additional spending. . . .
Practice research. The course organiser.
Authors: M J Whitfield, R C Hughes
Journal: BMJ (1981)

In 1965 one of us sent a questionnaire to all 142 trainee general practitioners in England and Wales.' In 1980 we made a survey of all 175 course organisers in England and Wales who are now arranging courses for over 2000 trainees?such has been the growth of vocational training for general practice over the past 15 years. Course organisers have been in existence since the early 1970s and arc paid at the same rate as are trainers in general practice but cannot be paid in addition for having a trainee in their practice. They arc appointed by the regional general practice advisory subcommittees of university regional postgraduate committees. Their main function is to run half-day or whole-day release courses that are attended usually weekly during university terms by trainees. Some also select trainers and trainees, organise trainer workshops, and assess training. At a conference in 1980, attended by almost half of the course organisers in Britain, it became clear that course organisers in each of the 15 regions in England and Wales perform many different functions, and we decided to survey all course organisers to find out their patterns of work and their opinions.
Human Accessory Cells Activate Fresh, Normal, Tumor&amp;ndash;Distant T Lymphocytes But Not Tumor&amp;ndash;Infiltrating T Lymphocytes to Lyse Autologous Tumor Cells in a Primary Cytotoxic T Lymphocyte Assay in Renal Cell Carcinoma
Authors: Gero Kramer, Georg E. Steiner, Sabine Paiha, Alessandra Handisurya, Bob Djavan, Roberto Mallone, Michael Marberger
Journal: European Urology (2001)
Observations on Renal Scanning and Intravenous Urography in Acute Segmental Renal Infarction
Authors: ROBERT LISBONA, VILMA DERBEKYAN, LEONARD ROSENTHALL
Journal: Clinical Nuclear Medicine (1981)

Nine patients with acute segmental renal infarction were examined by renal scanning and excretory urograms. The diagnosis of segmental infarction by intravenous urography is difficult. Radionuclide imaging is the preferred noninvasive method for demonstrating and sizing the renal infarct.
Prolapse. I. Aetiology and diagnosis.
Authors: J A Stallworthy
Journal: BMJ (1971)

Old age has no monopoly of prolapse, but it has a major interest in it. For example, at Oxford there are 1,00 women of all ages waiting for gynaecological surgery and 20% of these have prolapse. Each year about 400 patients are operated on for this condition, but as reported by A. C. W. Lewis the incidence of major degrees of prolapse requiring surgery is much higher in the older age groups.' He reviewed a ten-year period ending on 1 January 1967, during which over 12,000 major gynaecological operations were performed. Of these, 310 (nearly 3%) were on patients aged 70-90, 190 (61%) of them being for prolapse. The truss which supports grandfather's inguinal hernia fills
Diversity of Reproductive Tract Abnormalities in Men With Cystic Fibrosis
Authors: Michael Wilschanski
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The majority of adult men with cystic fibrosis (CF) are reportedly azoospermic due to congenital bilateral agenesis of the vas deferens (CBAVD), and this genital phenotype has been proposed as a diagnostic criterion for CF.<sup>1,2</sup>We evaluated the reproductive tract of men with CF using the following procedures: genital examinations by a specialist blinded to the patients' phenotypes and genotypes; hormone analyses (prolactin, follicle-stimulating hormone, luteinizing hormone, and testosterone); semen analyses (twice); and testicular and transrectal sonography. Genotype data were available from a previous study. Twenty-three men consented, and 20 completed all of the investigations, including 14 patients who were pancreatic insufficient (mean age, 29 years) and 6 who were pancreatic sufficient (mean age, 34 years). Thirty-five percent were homozygous for △<i>F</i>508, and 4 of 6 patients who were pancreatic sufficient had at least 1 mild gene mutation. Secondary sexual characteristics, testicular size, and
Abstract 5063: Matrilysin cleavage of perlecan produces bioactive fragments acting as a molecular switch to alter prostate cancer cell behavior.
Authors: Brian J. Grindel
Journal: Cancer Research (2013)

Abstract Perlecan/HSPG2[PLN], a large heparan sulfate (HS) proteoglycan, is expressed in the basement membrane (BM) underlying epithelial and endothelial cells. During prostate cancer (PCa) cell invasion, a variety of proteolytic enzymes are expressed that digest BM components including PLN. After proteolysis, fragments of PLN can be released into circulation. A sandwich ELISA with antibodies generated across PLN detected fragments of PLN from IG-repeat domain IV in PCa patient serum. An enzyme upregulated in invasive PCa cells, matrilysin/matrix metalloproteinase-7 (MMP-7), was examined as a candidate for PLN proteolysis both in silico and in vitro. Purified PLN showed high sensitivity to MMP-7 digestion even when fully decorated with HS or when embedded with other BM proteins. MMP-7 fragments of PLN were detected as limit peptides by western blot. While not predicted in silico, MMP-7 cleaved every subpart of recombinantly generated PLN domain IV. The resultant MMP-7 generated PLN Dm IV fragments were identified by mass spectrometry (LC-MS/MS and MALDI) and Edman degradation N-terminal sequencing. Other PCa relevant enzymes had limited ability to cleave PLN including prostate specific antigen, hepsin and fibroblast activation protein. To determine if PLN digestion affects metastatic PCa cells, C4-2B cells were seeded on plates coated with different forms of PLN. Cells on intact PLN formed large clusters of poorly adherent cells, while those on PLN digested with MMP-7 or heparitinase to remove the HS chains attached and spread within 30 minutes. Immunohistochemistry of PCa patient tissue indicates MMP-7 and PLN are in direct contact at interfaces in the stroma. We conclude that enzymatic processing of PLN in the BM and stroma as occurs in the tumor microenvironment can alter PCa cell behavior and favor cell dispersion and invasiveness. Citation Format: Brian J. Grindel. Matrilysin cleavage of perlecan produces bioactive fragments acting as a molecular switch to alter prostate cancer cell behavior. [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 5063. doi:10.1158/1538-7445.AM2013-5063
Allergen-induced generation of mediators in the mucosa.
Authors: S Mattoli
Journal: Environmental Health Perspectives (2001)

The inhalation of antigens does not normally lead to allergic inflammation, but airway resident cells and their products may affect the outcome of antigen exposure. It is therefore important to elucidate how potential allergens interact with airway epithelial cells and other cells located within and below the epithelium. Some studies have indicated that certain antigens, particularly the major house dust mite antigen Der p1, penetrate the airway epithelium by intracellular transportation or paracellular passage, depending on their concentrations, time of exposure, and ability of the cells to inactivate them. If an antigen possesses proteolytic activity, such as Der p1, and it reaches high concentrations or the exposure is prolonged, the disruption of the tight junction can also favor the transepithelial passage of other antigens. In this way, the antigens can easily encounter the effector cells located between epithelial cells and below the basement membrane. The magnitude of this phenomenon may be more prominent in the airways of asthmatic patients, as their epithelium is more permeable to Der p1 than the epithelium of nonasthmatic patients and releases cytokines after exposure to very low concentrations of this antigen for brief periods. Epithelial cell activation may facilitate the development of allergic mucosal sensitization to Der p1 and contribute to the antigen-induced inflammatory response by affecting the migration and function of dendritic cells, mast cells, and eosinophils. Also, there might be a secondary release of interleukin-6 and endothelin-1, which can have a detrimental effect on the cardiovascular function.
Herbal Aconite Tea and Refractory Ventricular Tachycardia
Authors: Lisa Lowe, Michael J. Matteucci, Aaron B. Schneir
Journal: New England Journal of Medicine (2005)

To the Editor: Recently, a patient presented to our emergency department with severe poisoning after ingesting an aconite-containing tea with therapeutic intent. Her course highlights the potentially great danger of ingesting such a preparation. The patient, a 66-year-old woman without known cardiac disease, obtained the herb for treatment of her osteoarthritis from a local herbalist, who instructed her to prepare it by making a tea. Approximately 90 minutes after ingestion of the tea, facial and extremity paresthesias developed, after which nausea, generalized weakness, and chest pressure rapidly developed. On arrival at our emergency department, she was found to have a . . .
Electrical Stimulation of the Heart in Patients with Ventricular Tachycardia
Authors: HEIN J. WELLENS, REINIER M. SCHUILENBURG, DIRK DURRER
Journal: Circulation (1972)

The initiation and termination of tachycardias were studied in five patients who suffered from recurrent attacks of ventricular tachycardia. In four, coronary artery disease with old myocardial infarction was present. A ventricular tachycardia could be initiated in all patients by a single right ventricular premature beat given during regular driving of the right ventricle. The tachycardia could be terminated by a single right ventricular premature beat, or two right ventricular premature beats given in close succession. In four of our patients an early right ventricular premature beat was followed by the next QRS complex of the tachycardia after an interval shorter than compensatory. Our results favor reentry as the causal mechanism for the tachycardias in our patients. Possible pathways for circus reentry leading to ventricular tachycardia can theoretically be composed of (1) the bundle branches, (2) Purkinje fibers with or without adjacent ventricular myocardium, (3) infarcted or fibrotic ventricular tissue, and (4) combinations of (1), (2), and (3).
Randomized Comparisons of Radiotherapy and Nitrosoureas for the Treatment of Malignant Glioma after Surgery
Authors: Michael D. Walker, Sylvan B. Green, David P. Byar, Eben Alexander, Ulrich Batzdorf, William H. Brooks, William E. Hunt, Collin S. MacCarty, M. Stephen Mahaley, John Mealey, Guy Owens, Joseph Ransohoff, James T. Robertson, William R. Shapiro, Kenneth R. Smith, Charles B. Wilson, Thomas A. Strike
Journal: New England Journal of Medicine (1980)

Within three weeks of definitive surgical intervention, 467 patients with histologically proved malignant glioma were randomized to receive one of four treatment regimens: semustine (MeCCNU), radiotherapy, carmustine (BCNU) plus radiotherapy, or semustine plus radiotherapy. We analyzed the data for the total randomized population and for the 358 patients in whom the initial protocol specifications were met (the valid study group). Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy. Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone. The group receiving carmustine plus radiotherapy had the best survival, but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant. The combination of carmustine plus radiotherapy produced a modest benefit in long-term (18-month) survival as compared with radiotherapy alone, although the difference between survival curves was not significant at the 0.05 level. This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy. (N Engl J Med. 1980; 303:1323–9.)
Autoimmune hepatitis in Brazilian patients is not linked to tumor necrosis factor α polymorphisms at position −308
Authors: Paulo Lisboa Bittencourt, Selma Aliotti Palácios, Eduardo Luiz Rachid Cançado, Gilda Porta, Sandra Drigo, Flair José Carrilho, Antonio Atı́lio Laudanna, Jorge Kalil, Anna Carla Goldberg
Journal: Journal of Hepatology (2001)
Tuberculosis Case-finding by Tuberculin-testing of Infant-school Children
Authors: I. A. MacDougall, J. R. Mikhail, W. H. Tattersall
Journal: BMJ (1953)

It has been notable that the response of cases of lymphoid leukaemia has been better than that of the myeloid cases.This is probably true even when allowances are made for the small numbers and the varied clinical condition of the patients.This finding has been encourag- ing, since with most other therapeutic agents the re- sponse of lymphoid leukaemia has been less favourable than that of myeloid leukaemia.Tests of renal and hepatic function have not revealed changes after treatment, and post-mortem examinations, although often demonstrating long-standing damage or infiltration by disease, have not shown signs which could be definitely interpreted as due to toxic effects from treatment.The haemopoietic system is highly sensitive to triethy- lene melamine, the effects being seen on the lymphocytes, granulocytes, and platelets of the peripheral blood.The simplification of dosing by oral administration of enteric-coated tablets has seemed to be a worth-while advance; nevertheless by its very simplicity it carries a certain danger of being used without the essential haematological controls.
Randomized Double-Blind Trial of Estrogen Replacement Therapy Versus Placebo in Stage I or II Endometrial Cancer: A Gynecologic Oncology Group Study
Authors: Richard R. Barakat, Brian N. Bundy, Nick M. Spirtos, Jeffrey Bell, Robert S. Mannel
Journal: Journal of Clinical Oncology (2006)

To determine the effect of estrogen replacement therapy (ERT) on recurrence rate and survival in women who have undergone surgery for stage I or II endometrial cancer.After surgery, eligible patients were allocated to therapy with ERT or placebo after undergoing hysterectomy with or without pelvic and aortic nodal sampling. Planned duration of hormonal versus placebo treatment was 3 years, with an additional 2 years of follow-up.The median follow-up time for all 1,236 eligible and assessable patients was 35.7 months. Stage, grade, histologic subtype, and percentage of patients receiving adjuvant therapy were similarly distributed between the groups. The median age at diagnosis for the 618 patients randomly assigned to ERT was 57 years (range, 26 to 91 years). Two hundred fifty-one patients (41.1%) were compliant with ERT for the entire treatment period. Disease recurrence was experienced in 14 patients (2.3%). Eight patients (1.3%) developed a new malignancy. There were 26 deaths (4.2%), and five deaths (0.8%) were a result of endometrial cancer. The median age at diagnosis for the 618 patients in the placebo group was 57 years (range, 30 to 88 years). Twelve patients (1.9%) experienced disease recurrence. Ten patients (1.6%) developed a new malignancy. There were 9 deaths (3.1%) in the placebo group, and four deaths (0.6%) were a result of endometrial cancer.Although this incomplete study cannot conclusively refute or support the safety of exogenous estrogen with regard to risk of endometrial recurrence, it is noteworthy that the absolute recurrence rate (2.1%) and the incidence of new malignancy were low.
1256 DIETARY SUPPLEMENTATION WITH OLIVE OIL WITH OR WITHOUT N-3 PUFA DIFFERENTIALLY AFFECTS INFLAMMATION AND PROGRESSION OF EXPERIMENTAL NONALCOHOLIC STEATOHEPATITIS
Authors: A. Provenzano, S. Milani, F. Vizzutti, W. Delogu, N. Navari, E. Novo, G. Laffi, M. Parola, F. Marra
Journal: Journal of Hepatology (2012)
ON PRECIPITABLE SUBSTANCES DERIVED FROM BACILLUS TYPHOSUS AND BACILLUS PARATYPHOSUS B
Authors: J. Furth, K. Landsteiner
Journal: The Journal of Experimental Medicine (1928)

Attempts to confirm certain statements that ether-soluble specific substances can be obtained from B. typhosus have lead to negative results. Two serologically active protein substances and another that was non-protein have been separated from B. typhosus. The first two are not resistant to tryptic digestion or to treatment with alkaline hypochlorite solution whereas the third resists both. One of the proteins could be extracted with 75 per cent alcohol. Specific precipitable substances reacting like the non-protein substance of B. typhosus and containing large amounts of carbohydrates have been prepared from B. paratyphosus B, B. enteritidis, and Proteus HX19 and OX19. Observations on the serological behaviour of these preparations are described.
Antibody to Aquaporin 4 in the Diagnosis of Neuromyelitis Optica
Authors: Friedemann Paul, Sven Jarius, Orhan Aktas, Martin Bluthner, Oliver Bauer, Heribert Appelhans, Diego Franciotta, Roberto Bergamaschi, Edward Littleton, Jacqueline Palace, Hans-Peter Seelig, Reinhard Hohlfeld, Angela Vincent, Frauke Zipp
Journal: PLoS Medicine (2007)

Neuromyelitis optica (NMO) is a demyelinating disease of the central nervous system (CNS) of putative autoimmune aetiology. Early discrimination between multiple sclerosis (MS) and NMO is important, as optimum treatment for both diseases may differ considerably. Recently, using indirect immunofluorescence analysis, a new serum autoantibody (NMO-IgG) has been detected in NMO patients. The binding sites of this autoantibody were reported to colocalize with aquaporin 4 (AQP4) water channels. Thus we hypothesized that AQP4 antibodies in fact characterize NMO patients.Based on these observations we cloned human water channel AQP4, expressed the protein in a eukaryotic transcription/translation system, and employed the recombinant AQP4 to establish a new radioimmunoprecipitation assay (RIPA). Indeed, application of this RIPA showed that antibodies against AQP4 exist in the majority of patients with NMO (n = 37; 21 positive) as well as in patients with isolated longitudinally extensive transverse myelitis (n = 6; six positive), corresponding to a sensitivity of 62.8% and a specificity of 98.3%. By contrast, AQP4 antibodies were virtually absent in 291 other participants, which included patients with MS (n = 144; four positive), patients with other inflammatory and noninflammatory neurological diseases (n = 73; one positive), patients with systemic autoimmune diseases (n = 45; 0 positive), and healthy participants (n = 29; 0 positive).In the largest series reported so far to our knowledge, we quantified AQP4 antibodies in patients with NMO versus various other diseases, and showed that the aquaporin 4 water channel is a target antigen in a majority of patients with NMO. The newly developed assay represents a highly specific, observer-independent, and easily reproducible detection method facilitating clinically relevant discrimination between NMO, MS, and other inflammatory diseases.
NEOINTIMAL TISSUE CLASSIFICATION USING OPTIMAL COHERENCE TOMOGRAPHY AFTER PACLITAXEL-COATING BALLOON TREATMENT IN PIG IN-STENT STENOSIS MODEL
Authors: Arihiro Sumida, Hiroyuki Nagai, Bill Gogas, Jinsheng Li, Jaipal Singh, Spencer King, Nicolas Chronos, Dongming Hou
Journal: Journal of the American College of Cardiology (2012)