tbuckley/cabot-search huggingface dataset:
Accuracy of Central Benzodiazepine Receptor Binding Potential/Cerebral Blood Flow SPECT Imaging for Detecting Misery Perfusion in Patients With Unilateral Major Cerebral Artery Occlusive Diseases
Authors: Hiroki Kuroda, Kuniaki Ogasawara, Taro Suzuki, Kohei Chida, Kenta Aso, Masakazu Kobayashi, Kenji Yoshida, Kazunori Terasaki, Shunrou Fujiwara, Yoshitaka Kubo, Akira Ogawa
Journal: Clinical Nuclear Medicine (2012)

The aim of the present study was to determine whether central benzodiazepine receptor binding potential (BRBP)/cerebral blood flow (CBF) or a combination of CBF and cerebrovascular reactivity (CVR) to acetazolamide on single-photon emission computed tomography (SPECT) more accurately detects misery perfusion, indicating elevation of absolute value of oxygen extraction fraction (OEF) on positron emission tomography (PET), in patients with unilateral major cerebral artery occlusive diseases.In 84 patients, OEF, CBF, CVR to acetazolamide, and BRBP were assessed using ¹⁵O-PET and N-isopropyl-p-[¹²³I]-iodoamphetamine and [¹²³I]-iomazenil SPECT, respectively. A region of interest was automatically placed in the middle cerebral artery territory using a 3-dimensional stereotactic region of interest template.Sensitivity, specificity, and positive and negative predictive values for the affected side-to-contralateral side asymmetry on SPECT-BRBP/CBF to detect the abnormally elevated PET-OEF in the affected hemisphere were 100%, 86.4%, 66.7%, and 100%, respectively. Area under the receiver operating characteristic curve in detecting the abnormally elevated PET-OEF in the affected hemisphere did not differ between analysis of the combination of SPECT-CBF and SPECT-CVR in the affected hemisphere (0.89; 95% confidence interval, 0.80-0.94) and that of the affected side-to-contralateral side asymmetry on SPECT-BRBP/CBF (0.93; 95% confidence interval, 0.86-0.97). The combination of the 3 detected abnormally elevated PET-OEF with 97.0% specificity and 90.0% positive predictive value.The accuracy of central BRBP/CBF asymmetry on SPECT is equivalent to that of the combination of CBF and CVR to acetazolamide on SPECT for detecting misery perfusion in patients with unilateral major cerebral artery occlusive disease.
Abstract 245: ST6Gal-I sialylation of the Fas (CD95) receptor provides protection against Fas mediated apoptosis
Authors: Amanda F. Swindall, Zhongyu Liu, Susan L. Bellis
Journal: Cancer Research (2012)

Abstract The golgi glycosyltransferase, ST6Gal-I, adds the negatively-charged sugar, α2-6 sialic acid to membrane and secreted proteins. This enzyme has been shown to be upregulated in numerous human cancers including colon cancer. However, the function of ST6Gal-I in tumor progression remains unclear due to a dearth of knowledge regarding enzyme substrates, and the effect of sialylation on target function. Previously, we have shown ST6Gal-I to be upregulated by oncogenic-ras which leads to increased invasion in colon carcinoma cells. Recently a role for ST6Gal-I in the protection of tumors against apoptosis is emerging, as we have shown sialylation to block galectin-mediated apoptosis by inhibiting the binding of galectin-3. Here we identify the Fas (CD95) receptor as a target for ST6Gal-I sialylation, and show that Fas sialylation prohibits apoptotic signaling in two independent cell models. Specifically, in an shRNA knockdown of ST6Gal-I in cells with high endogenous ST6Gal-I (HD3), and in a forced expression of ST6Gal-I in cells with no endogenous sialyltransferases (SW48), we show the presence of ST6Gal-I impedes Fas apoptotic signaling. Upon treatment with both the activating antibody, CH11 and the endogenous ligand, FasL, cells expressing ST6Gal-I had decreased levels of cleaved caspases 3 and 8, as shown by western blot and immunofluorescent staining. However, there was no difference in DR4/DR5-mediated apoptosis induced by TRAIL, suggesting a specific effect of ST6Gal-I on Fas-mediated apoptosis. Additionally, we have shown ST6Gal-I sialylation of Fas decreases the binding of FADD to Fas cytoplasmic tails limiting DISC formation, and prohibits receptor internalization after activation, effectively blocking Fas apoptotic signaling. We have also shown Fas-mediated apoptosis driven by the agonistic antibody, Jo2, to be inhibited in primary macrophages from transgenic mice genetically engineered by our lab to over-express ST6Gal-I. Furthermore, we have shown ST6Gal-I to be upregulated in 7/9 human colon tumor samples, and despite Fas downregulation, the expressed Fas is hypersialylated in several human tumor tissues. In summary, these data identify ST6Gal-I sialylation of the Fas receptor as a novel mechanism in the self-protection of tumors against apoptosis, and further identify ST6Gal-I as an important regulator of apoptotic signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 245. doi:1538-7445.AM2012-245
Laparoscopic cholecystectomy as a safe and effective treatment for severe acute cholecystitis.
Authors: R. G. Wilson, I. M. Macintyre, S. J. Nixon, J. H. Saunders, J. S. Varma, P. M. King
Journal: BMJ (1992)

To evaluate the feasibility and safety of laparoscopic cholecystectomy in severe acute cholecystitis.Analysis of data collected prospectively from a consecutive series of 350 laparoscopic operations.Two general surgical units in a teaching hospital.31 patients with a diagnosis of severe acute cholecystitis based on clinical examination, investigation results, and operative findings.Initial intravenous fluids and broad spectrum antibiotics followed by laparoscopic cholecystectomy within 72 hours of presentation.Failure to complete the operation laparoscopically, length of postoperative stay in hospital, early postoperative morbidity, interval from operation to full activity, and return to work.Laparoscopic cholecystectomy was attempted in 19 patients with empyema of the gall bladder and 12 who had severe cholecystitis which failed to settle on medical management. A total of 29 operations were successfully completed with two conversions to open surgery. Two minor postoperative complications occurred, and one case of retained common bile duct stones with jaundice was treated by endoscopic retrograde cholangiopancreatography and papillotomy. Median postoperative hospital stay was two days, with return to normal activity in seven days and to work in two weeks. There were no deaths related to the operation.In the presence of severe acute cholecystitis laparoscopic cholecystectomy is feasible in most patients, with minimal risk of injury to surrounding structures and considerable benefits. It is recommended that laparoscopic cholecystectomy should be attempted in these patients when appropriate surgical skill is available.
Influenza vaccination and the elderly.
Authors: I R Wakefield
Journal: BMJ (1990)

is therefore unclear, but screening certainly merits consideration given the cost of long term antiandrogen therapy for hirsutism compared with that of dexamethasone.A diagnosis of 21 -hydroxylase deficiency would prevent the patient from being exposed to the potential adverse effects of long term treatment and may also avoid the necessity for infertility treatment.
A New Arthritis Therapy with Oxidative Burst Inducers
Authors: Malin Hultqvist, Peter Olofsson, Kyra A Gelderman, Jens Holmberg, Rikard Holmdahl
Journal: PLoS Medicine (2006)

Background Despite recent successes with biological agents as therapy for autoimmune inflammatory diseases such as rheumatoid arthritis (RA), many patients fail to respond adequately to these treatments, making a continued search for new therapies extremely important. Recently, the prevailing hypothesis that reactive oxygen species (ROS) promote inflammation was challenged when polymorphisms in Ncf1, that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. Based on these findings we developed a new therapy for arthritis using oxidative burst-inducing substances. Methods and Findings Treatment of rats with phytol (3,7,11,15-tetramethyl-2-hexadecene-1-ol) increased oxidative burst in vivo and thereby corrected the effect of the genetic polymorphism in arthritis-prone Ncf1DA rats. Importantly, phytol treatment also decreased the autoimmune response and ameliorated both the acute and chronic phases of arthritis. When compared to standard therapies for RA, anti-tumour necrosis factor-α and methotrexate, phytol showed equally good or better therapeutic properties. Finally, phytol mediated its effect within hours of administration and involved modulation of T cell activation, as injection prevented adoptive transfer of disease with arthritogenic T cells. Conclusions Treatment of arthritis with ROS-promoting substances such as phytol targets a newly discovered pathway leading to autoimmune inflammatory disease and introduces a novel class of therapeutics for treatment of RA and possibly other chronic inflammatory diseases.
Nifedipine: a new treatment for perniosis
Authors: M.H.A. Rustin, J.A. Newton, P.M. Dowd
Journal: British Journal of Dermatology (1987)

Perniosis consists of inflammatory cutaneous lesions, usually arising on acral sites as a result of an abnormal reaction to cold. Spontaneous resolution occurs, but some patients have chronic, recalcitrant and ulcerating lesions which persist into the summer. Although the aetiology is unknown, there are features suggesting a vasospastic component and since nifedipine is an effective treatment of Raynaud's phenomenon, we wondered whether it might also be beneficial in another cold-related disorder, perniosis. Twenty-five patients (23 female, two male) with severe recalcitrant perniosis were enrolled into an open study; 22 had idiopathic perniosis, three had associated anorexia nervosa.1 Nifedipine retard 20 mg was prescribed after onset of lesions and the dose was increased by increments of 20 mg every 3 days until a therapeutic dose was achieved or side-effects developed. Seventeen patients experienced rapid symptomatic relief on a modal dose of 60 mg daily with clearing of lesions after a mean of 14 days. A comparison of pre- and post-treatment biopsies showed resolution of the dermal oedema and diminution of the perivascular cellular infiltrate. Six patients who derived no benefit only achieved a dose of 30 mg daily because of side-effects and two patients were lost to follow-up. There was no correlation between the aetiology, clinical and histological features and response to treatment.
Regulation of antioxidant enzymes in lung after oxidant injury.
Authors: T Quinlan, S Spivack, B T Mossman
Journal: Environmental Health Perspectives (1994)

Studies have implicated active oxygen species (AOS) in the pathogenesis of various lung diseases. Many chemical and physical agents in the environment are potent generators of AOS, including ozone, hyperoxia, mineral dusts, paraquat, etc. These agents produce AOS by different mechanisms, but frequently the lung is the primary target of toxicity, and exposure results in damage to lung tissue to varying degrees. The lung has developed defenses to AOS-mediated damage, which include antioxidant enzymes, the superoxide dismutases [copper-zinc (CuZnSOD) and manganese-containing (MnSOD)], catalase, and glutathione peroxidase (GPX). In this review, antioxidant defenses to environmental stresses in the lung as well as in isolated pulmonary cells following exposure to a number of different oxidants, are summarized. Each oxidant appears to induce a different pattern of antioxidant enzyme response in the lung, although some common trends, i.e., induction of MnSOD following oxidants inducing inflammation or pulmonary fibrosis, in responses to oxidants occur. Responses may vary between the different cell types in the lung as a function of cell-cycle or other factors. Increases in MnSOD mRNA or immunoreactive protein in response to certain oxidants may serve as a biomarker of AOS-mediated damage in the lung.
Men behaving madly
Authors: G. Adshead
Journal: BMJ (2009)

Folate cofactors are one-carbon donors essential for the biosynthesis of purines and thymidylate. Mammalian cells are devoid of folate biosynthesis and are therefore folate auxotrophs that take up folate vitamins primarily via the reduced folate carrier (RFC). In this study, we showed that the human RFC (hRFC) gene can serve as a novel selectable marker for the overproduction of recombinant proteins. Toward this end, a hemagglutinin (HA) epitope tagged hRFC (hRFC-HA) was introduced into a bicistronic vector (pIRES2-EGFP), upstream of an enhanced green fluorescent protein (EGFP) reporter gene. Chinese hamster ovary cells deficient in RFC activity were isolated and transfected with this construct, followed by gradual deprivation of leucovorin, the sole folate source in the growth medium. Only cells with hRFC-HA overexpression were able to take up leucovorin and thereby survive these selective conditions. Western blot and immunofluorescence analyses confirmed that the hRFC-HA was overexpressed at extremely high levels, properly glycosylated and sorted out to the plasma membrane. This resulted in a ∼450-fold increase in [<sup>3</sup>H]methotrexate influx and ∼100-fold increased sensitivity to methotrexate, relative to untransfected RFC-deficient cells. Flow cytometric analysis consistently revealed that EGFP was overexpressed ∼100-fold above the autofluorescence level. Overproduction of hRFC-HA and EGFP was stably maintained for at least 2 months in a constant concentration of leucovorin. These results establish a novel RFC-based metabolic selection system for the efficient overexpression of recombinant proteins. Furthermore, the possible implications to subcellular transporter localization and restoration of MTX sensitivity in drug-resistant tumors by RFC-based gene therapy are discussed.
Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells
Authors: Leonie Beljaars, Grietje Molema, Betty Weert, Harmke Bonnema, Peter Olinga, Geny M. Groothuis, Dirk K. Meijer, Klaas Poelstra
Journal: Hepatology (1999)

The hallmark of liver fibrosis is an increased extracellular matrix deposition, caused by an activation of hepatic stellate cells (HSC). Therefore, this cell type is an important target for pharmacotherapeutic intervention. Antifibrotic drugs are not efficiently taken up by HSC or may produce unwanted side-effects outside the liver. Cell-specific delivery can provide a solution to these problems, but a specific drug carrier for HSC has not been described until now. The mannose 6-phosphate/insulin-like growth factor II (M6P/IGF-II) receptor, which is expressed in particular upon HSC during fibrosis, may serve as a target-receptor for a potential carrier. The aim of the present study was to examine if human serum albumin (HSA) modified with mannose 6-phosphate (M6P) is taken up by HSC in fibrotic livers. A series of M6Px -modified albumins were synthetized: x = 2, 4, 10, and 28. Organ distribution studies were performed to determine total liver uptake. The hepatic uptake of M6Px-HSA increased with increasing M6P density. M6Px-HSA with a low degree of sugar loading (x = 2-10) remained in the plasma and accumulated for 9% ± 0.5% or less in fibrotic rat livers. An increase in the molar ratio of M6P:HSA to 28:1 caused an increased liver accumulation to 59% ± 9% of the administered dose. Furthermore, we determined quantitatively the in vivointrahepatic distribution of M6Px-HSA using double-immunostaining techniques. An increased substitution of M6P was associated with an increased accumulation in HSC; 70% ± 11% of the intrahepatic staining for M6P28-HSA was found in HSC. We also demonstrate that M6P-modified bovine serum albumin (BSA) accumulates in slices of normal and cirrhotic human livers. After incubation of this neoglycoprotein with human tissue, the protein is found in nonparenchymal liver cells. Because M6P-modified albumins are taken up by HSC in fibrotic livers, this neoglycoprotein can be applied as a selective drug carrier for HSC. This technology may create new opportunities for the pharmacological intervention of liver fibrosis
Effects of Exposure to Factor Concentrates Containing Donations From Identified AIDS Patients
Authors: Janine Jason
Journal: JAMA (1986)

We compared recipients of eight lots of factors VIII and IX voluntarily withdrawn from distribution because one donor was known to have subsequently developed the acquired immunodeficiency syndrome with a nonexposed cohort matched by age, sex, and factor use. The factor VIII recipient cohorts did not differ in prevalence of antibody to human immunodeficiency virus (HIV) (exposed, 75%; nonexposed, 86%), T-cell subset numbers (median: exposed, 619 T-helper cells per cubic millimeter; nonexposed, 659 T-helper cells per cubic millimeter), T-helper to T-suppressor ratios, or immunoglobulin levels. Exposed individuals had higher levels of immune complexes by C1q binding and staphylococcal binding assays and lower responses to phytohemagglutinin and concanavalin A. However, only the staphylococcal binding assay values were outside the normal range for our laboratory. Factor IX recipient cohorts did not differ in HIV antibody prevalence (exposed, 30%; nonexposed, 40%) or any immune tests. Although exposed and nonexposed individuals did not differ from each other in a clinically meaningful fashion at initial testing, both the exposed and nonexposed cohorts had high rates of HIV seroprevalence. Market withdrawals were clearly insufficient means of limiting the spread of HIV in hemophilic patients; however, the currently available methods of donor screening and viral inactivation of blood products will prevent continued exposure within this population.
Combination therapies augment the anti-tumor activity of agonist CD27 mAb in human CD27 transgenic mouse models
Authors: Li-Zhen He, Lawrence J Thomas, James Testa, Jeffrey Weidlick, Crystal Sisson, Russell Hammond, Laura Vitale, Henry Marsh, Tibor Keler
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts CDX-1127 is a fully human antibody to CD27, a TNF receptor superfamily member expressed on the majority of T cells and subsets of NK cells and B cells. We have previously characterized the co-stimulatory activities of CDX-1127 with human T cell cultures and a human CD27 transgenic
On the Use of Cantharidinate of Potash in the Treatment of Pulmonary Tuberculosis
Authors: W. S. Fenwick, A. G. Welsford
Journal: BMJ (1891)

was felt to end abruptly in a firmi hiard pipe-like piece of bowel about as thtick as the thuimtb ;thlis wvas tighitly bouno( downi to the brinii of Ilie pel- vis by denise 411brou-s tissue.It was at onice obvious, oni this-examinaftion, that, owvine hi time demise fibrous tissue inito whichl the coats of tise bowel hiad beeni conver,ted, aniv oper ation oni the stiictured pairt itself wNas hio
Bacteroides fragilis Subspecies in Clinical Isolates
Authors: B. FRANK POLK
Journal: Annals of Internal Medicine (1977)

Isolates of Bacteroides fragilis from 83 infected patients were collected during 2 years. Of 103 isolates, 68% were subspecies fragilis. This was the single most common subspecies isolated from blood (12/17), intra-abdominal (11/28), wound (17/20), perirectal (11/16), pelvic (6/10), and other (8/11) sites. Sixteen patients had B. fragilis isolated in pure culture. Of these, 9/12 blood cultures and 4/4 cultures from other sites were ss. fragilis. The recent observation that ss. fragilis organisms are encapsulated whereas the other subspecies are generally unencapsulated was supported by indirect fluorescent antibody studies using antibodies prepared to the capsular material of ss. fragilis. All 33 strains of ss. fragilis and none of 13 strains of other subspecies were positive. The predominance of ss. fragilis in clinical isolates compared to its relative infrequency in normal fecal flora and its predominance in pure cultures, especially of blood, indicate that this is the most virulent of B. fragilis subspecies. This virulence may be related to encapsulation.
The Nurse-Physician Relationship
Authors: Robert B. Sklaroff
Journal: Annals of Internal Medicine (1990)

Letters and Corrections15 June 1990The Nurse-Physician RelationshipRobert B. Sklaroff, MD, Susan A. Weiss, RN, MSN, Robert B. Sklaroff, MD, AssociatesRobert B. Sklaroff, MDSearch for more papers by this author, Susan A. Weiss, RN, MSNSearch for more papers by this author, Robert B. Sklaroff, MD, AssociatesSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-112-12-964_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: Ginzberg (1) neglected to discuss three generic approaches to alleviating the nursing shortage: nurse-designed strategy, nurse-physician collaboration, and physician-supported restructuring. Such efforts are being conducted both on a "micro" level and through professional societies; singly and collectively, they are based on the premise that a mature physician-nurse relationship provides the optimal controlling force in health care delivery and the sine qua non of any solution to this crisis: professional satisfaction."Hospitals and their physician staffs need to take action to ensure that nurses will be used effectively and at their highest level of competence," but it is...References1. Ginzberg E. What physicians should know about the nursing shortage. Ann Intern Med. 1990;112:319-20. LinkGoogle Scholar2. EthridgeLamb PG. Professional nursing case management improves quality, access and costs. Nursing Management. 1989;20:30-5. CrossrefMedlineGoogle Scholar3. SteinWattsHowell LDT. The doctor-nurse game revisited. N Engl J Med. 1990;322:546-9. CrossrefMedlineGoogle Scholar4. DiamondSklaroff SR. Collaborative practice in hematology-oncology. Oncology Nursing Forum. 1986;13(Suppl):73. Google Scholar5. Sklaroff R. Alleviating the nursing crisis by restructuring nursing education. In: Proceedings of the House of Delegates of the AMA, 43rd Interim Meeting (12/3/89-12/6/89). [Resolution #65] Chicago: American Medical Association; 1990 [In press]. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Elkins Park, PA 19117-2253 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 June 1990Volume 112, Issue 12Page: 964-964KeywordsHealth care Issue Published: 15 June 1990 PDF DownloadLoading ...