tbuckley/cabot-search huggingface dataset:
Shared idiotypes and restricted immunoglobulin variable region heavy chain genes characterize murine autoantibodies of various specificities.
Authors: M Monestier, A Manheimer-Lory, B Bellon, C Painter, H Dang, N Talal, M Zanetti, R Schwartz, D Pisetsky, R Kuppers
Journal: Journal of Clinical Investigation (1986)

The study of the Ig variable region heavy chain (VH) genes used to encode antibodies specific for self-epitopes from murine hybridomas showed that three VH families are primarily utilized: VH J558, the largest family, and VH QPC52 and VH 7183, the families most proximal to the Ig joining region heavy chain genes. These monoclonal autoantibodies express cross-reactive idiotopes shared by rheumatoid factors and antibodies specific for Sm. The expression of these idiotypes is independent of major histocompatibility complex and Ig constant region heavy chain haplotypes, self-antigen specificity, and even the VH gene family utilized. Though the experiments described here are limited to murine autoantibodies, similarities exist between murine and human autoimmune diseases. Studies that aim to investigate the relationship between VH gene expression and the presence of cross-reactive idiotypes among human autoantibodies should enable us to better understand the mechanisms of autoimmunity and self-tolerance.
Analysis of coagulation and fibrinolysis during intravenous infusion of recombinant human tissue-type plasminogen activator in patients with acute myocardial infarction.
Authors: D Collen, H Bounameaux, F De Cock, H R Lijnen, M Verstraete
Journal: Circulation (1986)

Coagulation and fibrinolysis were studied in patients with acute myocardial infarction during intravenous infusion of recombinant human tissue-type plasminogen activator (rt-PA) (0.75 mg/kg over 90 min, n = 101), streptokinase (1,500,000 IU over 60 min, n = 61), or placebo (n = 40). In the rt-PA group, the plasma level of rt-PA antigen was 1.2 +/- 0.6 micrograms/ml (mean +/- SD) and the euglobulin fibrinolytic activity (EFA) was 910 +/- 735 IU t-PA/ml. In the streptokinase group, the EFA was equivalent to 430 +/- 435 IU t-PA/ml. At the end of the infusion, the plasma fibrinogen level measured with a coagulation rate assay was decreased to 57 +/- 33% of the preinfusion value in the rt-PA group, to 7 +/- 10% in the streptokinase group, and remained unchanged in the placebo group. Fibrinogen-fibrin degradation products increased to 0.75 +/- 0.54 mg/ml in the streptokinase group but to only 0.10 +/- 0.13 mg/ml in the rt-PA group. The plasma levels of alpha 2-antiplasmin, plasminogen, and factor V decreased to between 30% and 45% in the rt-PA group but significantly more in the streptokinase group (to between 15% and 25%). Thus rt-PA induced much less systemic fibrinolytic activation than streptokinase. In the patients who received rt-PA, a weak correlation (r = .21, n = 89, .1 greater than p greater than .05) was found between the extent of fibrinogen breakdown at 90 min and the plasma rt-PA concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Neonatal alloimmune thrombocytopenia: Spontaneous in utero intracranial hemorrhage
Authors: Robert F. Burrows, Chris C. Caco, John G. Kelton
Journal: American Journal of Hematology (1988)

Abstract Neonatal alloimmune thrombocytopenia is an uncommon but important cause of thrombocytopenia in infants. Because of the severity of the thrombocytopenia, some of these infants will have intracranial hemorrhage with resultant long‐term disability. Obstetricians and neonatologists have recommended delivery by caesarean section and the rapid institution of appropriate treatment for the infant; however, it is theoretically possible that a hemorrhagic event could precede the delivery and consequently not be prevented by these perinatal interventions. In this report we describe a neonate in whom the diagnosis of alloimmune neonatal thrombocytopenia was suspected because of antenatal ultrasound evidence of intracerebral hemorrhage. This case demonstrates the importance of antenatal fetal assessment and indicates the need for the development of therapeutic strategies to maintain fetal hemostasis.
Quantitative Optical Imaging of Primary Tumor Organoid Metabolism Predicts Drug Response in Breast Cancer
Authors: Alex J. Walsh, Rebecca S. Cook, Melinda E. Sanders, Luigi Aurisicchio, Gennaro Ciliberto, Carlos L. Arteaga, Melissa C. Skala
Journal: Cancer Research (2014)

Abstract There is a need for technologies to predict the efficacy of cancer treatment in individual patients. Here, we show that optical metabolic imaging of organoids derived from primary tumors can predict the therapeutic response of xenografts and measure antitumor drug responses in human tumor–derived organoids. Optical metabolic imaging quantifies the fluorescence intensity and lifetime of NADH and FAD, coenzymes of metabolism. As early as 24 hours after treatment with clinically relevant anticancer drugs, the optical metabolic imaging index of responsive organoids decreased (P &amp;lt; 0.001) and was further reduced when effective therapies were combined (P &amp;lt; 5 × 10−6), with no change in drug-resistant organoids. Drug response in xenograft-derived organoids was validated with tumor growth measurements in vivo and staining for proliferation and apoptosis. Heterogeneous cellular responses to drug treatment were also resolved in organoids. Optical metabolic imaging shows potential as a high-throughput screen to test the efficacy of a panel of drugs to select optimal drug combinations. Cancer Res; 74(18); 5184–94. ©2014 AACR.
Older people may have to take out insurance to pay for long term care
Authors: H. Mooney
Journal: BMJ (2009)

Older people in England could be asked to take out insurance to pay for long term care in their old age, as one option proposed by the government in a green paper on reform of the funding arrangements for residential and home based social care.

Under the present English system anyone with a home or savings of £23 500 (€27 400; $38 200) or more is not given state funding for a care home or help from social services.

This means that thousands of pensioners each year have to sell their homes or use their …
ErbB2 Trafficking and Degradation Associated with K48 and K63 Polyubiquitination
Authors: Corina Marx, Jason M. Held, Bradford W. Gibson, Christopher C. Benz
Journal: Cancer Research (2010)

The overexpressed ErbB2/HER2 receptor is a clinically validated cancer target whose surface localization and internalization mechanisms remain poorly understood. Downregulation of the overexpressed 185-kDa ErbB2 receptor is rapidly (2-6 hours) induced by the HSP90 chaperone inhibitor geldanamycin (GA), whereas its downregulation and lysosomal degradation are more slowly (24 hours) induced by the proteasome inhibitor bortezomib/PS341. In PS341-treated SK-BR-3 cells, overexpressed ErbB2 coprecipitates with the E3 ubiquitin ligase c-Cbl and also with the deubiquitinating enzyme USP9x; moreover, siRNA downregulation of USP9x enhances PS341-induced ErbB2 downregulation. Because polyubiquitin linkages via lysine 48 (K48) or 63 (K63) can differentially address proteins for 26S proteasomal degradation or endosome trafficking to the lysosome, multiple reaction monitoring (MRM)/mass spectrometry (MS) and polyubiquitin linkage-specific antibodies were used to quantitatively track K48-linked and K63-linked ErbB2 polyubiquitination following either GA or PS341 treatment of SK-BR-3 cells. MRM/MS revealed that unlike the rapid, modest (4-fold to 8-fold), and synchronous GA induction of K48 and K63 polyubiquitinated ErbB2, PS341 produces a dramatic (20-fold to 40-fold) sequential increase in polyubiquitinated ErbB2 consistent with K48 polyubiquitination followed by K63 editing. Fluorescence microscopic imaging confirmed that PS341, but not GA, induces colocalization of K48-linked and K63-linked polyubiquitin with perinuclear lysosome-sequestered ErbB2. Thus, ErbB2 surface overexpression and recycling seem to depend on its polyubiquitination and deubiquitination; as well, the contrasting effects of PS341 and GA on ErbB2 receptor localization, polyubiquitination, and degradation point to alternate cytoplasmic trafficking likely regulated by different K48 and K63 polyubiquitin editing mechanisms.
Yttrium-90 Microsphere Radioembolization for Hepatocellular Carcinoma
Authors: Julien Edeline, Marine Gilabert, Etienne Garin, Eveline Boucher, Jean-Luc Raoul
Journal: Liver Cancer (2014)

Yttrium-90 (Y90) radioembolization is an emerging strategy to treat liver malignancies, and clinical data supporting its use have accumulated in recent years. Y90-radioembolization has shown clinical effectiveness in intermediate and advanced hepatocellular carcinoma, with a favorable safety profile. Retrospective data show similar levels of effectiveness to transarterial chemoembolization in intermediate hepatocellular carcinoma, with some evidence of better tolerance. While phase 3 studies comparing Y90-radioembolization to chemoembolization in intermediate hepatocellular carcinoma would be difficult to conduct, studies comparing or combining Y90-radioembolization with sorafenib are under way. Questions also remain about the most suitable modalities for defining the dose to administer. Phase 3 studies are under way to clarify the place of Y90-radioembolization in the algorithm of HCC treatment.
Risk Stratification for Bladder Tumor Recurrence, Stage and Grade by Urinary Nuclear Matrix Protein 22 and Cytology
Authors: Shahrokh F Shariat, Roberto Casella, Frank H Wians, Raheela Ashfaq, Jody Balko, Tullio Sulser, Thomas C Gasser, Arthur I Sagalowsky
Journal: European Urology (2003)
Monoclonal Immunoglobulin Deposition Disease: Light Chain and Light and Heavy Chain Deposition Diseases and Their Relation to Light Chain Amyloidosis
Authors: Joel N. Buxbaum
Journal: Annals of Internal Medicine (1990)

Monoclonal immunoglobulin deposition occurs in tissues as Congo Red binding fibrils in light chain amyloidosis, as less structured deposits in light chain deposition disease, and as similar but distinct deposits in light and heavy chain deposition disease. The nonamyloid forms were found in 13 patients who had evidence of plasmacytic dyscrasia by the immunohistochemical detection of immunoglobulin light chains of kappa or lambda class (with or without staining for a single heavy chain isotype) and by the absence of amyloid P component in tissue sections that did not show the birefringence characteristic of amyloid after Congo Red staining. All but two of the patients presented with proteinuria with or without azotemia. Clinical syndromes involving other organ systems were less common but occasionally severe. Four patients had overt multiple myeloma. Three others had hypercalcemia and mild bone marrow plasmacytosis but no lytic lesions. Analyses of immunoglobulin synthesis in bone marrow cells from seven patients showed excess light chains in all and incomplete light chains or heavy chain fragments in six, regardless of whether an intact monoclonal protein or related subunit was in the serum or urine. The fibrillar (amyloidotic) and nonfibrillar forms of monoclonal immunoglobulin deposition occur either in overt multiple myeloma or in the course of less neoplastically aggressive plasmacytic dyscrasias. Bone marrow cells from patients with either type produce immunoglobulin fragments that are related to those deposited in the affected tissues.
Pemetrexed with or without Matuzumab as Second-Line Treatment for Patients with Stage IIIB/IV Non-small Cell Lung Cancer
Authors: Joan H. Schiller, Joachim von Pawel, Philipp Schütt, Rafat H. Ansari, Michael Thomas, Mansoor Saleh, Robert D. McCroskey, Wolfgang Pfeifer, Thomas A. Marsland, Goetz H. Kloecker, Martin Sebastian, Robert Pirker, Raffael Kurek, Claire Beadman, Mark A. Socinski
Journal: Journal of Thoracic Oncology (2010)
The Natural History of Carotid Bruits in Elderly Persons
Authors: Jerome Van Ruiswyk
Journal: Annals of Internal Medicine (1990)

To determine the relative risk for cerebrovascular events in elderly patients with carotid bruits.Population-based prospective study.Community-based home for the aged.All patients were residents of a home for the aged and were at least 75 years old in 1985.Two hundred and forty-one residents were examined for carotid bruits and signs of previous stroke. The mean age of the residents was 86 years. Twelve percent of residents had asymptomatic carotid bruits. The prevalence of asymptomatic carotid bruits was 8% in residents who were 75 to 84 years of age, 10% in residents who were 85 to 94 years of age, and 13% in residents who were at least 95 years old. Interval cerebrovascular events and cause of death were ascertained from chart review, and recorded events in survivors were confirmed by a repeat examination. The 3-year cumulative incidence of cerebrovascular events in asymptomatic residents with carotid bruits was 10%, compared with 9% in residents without carotid bruits, yielding a relative risk of 1.1 (95% CI, 0.45 to 2.7). In 60% of surviving residents, baseline carotid bruits were no longer present at the time of follow-up examination. The disappearance of these bruits was not associated with the occurrence of interval cerebrovascular events.The prevalence of asymptomatic carotid bruits increases with advanced age. Carotid bruits do not greatly increase the risk for subsequent stroke in elderly patients. Carotid bruits may often disappear without clinical sequelae.
Physical Disabilities and the Study and Practice of Medicine
Authors: Carlos J. M. Martini
Journal: JAMA (1987)

Whether the number of physicians with functional limitations is about 18 000 as suggested by Zondlo<sup>1</sup>or close to 80 000 as indicated by the last figures from the National Institute of Handicapped Research,<sup>2</sup>the fact remains that a large number of the 552 000 physicians in the United States suffer from impaired motor skills. The true number may never be known. As Cathell<sup>3</sup>reminded us in 1924 in his<i>Book on the Physician Himself</i>, "medical men often conceal the fact that they are sickly or that their health is failing, as much and as long as possible," since they remember the old adage, "Do not trust to a sick physician." This perception may still keep physicians from revealing disabling conditions that they may be able to conceal. What matters, of course, is not the total number of physicians with physically disabling conditions, but the understanding of
The Patient Self-Determination Act and the Future of Advance Directives
Authors: Peter J. Greco, Kevin A. Schulman, Risa Lavizzo-Mourey, John Hansen-Flaschen
Journal: Annals of Internal Medicine (1991)

▪Living wills and other advance directives currently play a limited role in medical decision making. A new federal law, the Patient Self-Determination Act, will require health care providers in hospitals, nursing homes, and other facilities to inquire about the presence of advance directives, to record patient preferences in the medical record, and to develop institutional policies regarding the implementation of these directives. Unfortunately, the law does little to promote discussion or preparation of advance directives before hospitalization. Additional efforts to promote the use of advance directives can take place in the outpatient medical care system, in attorneys' offices, or through health insurers. Because most people have not yet prepared an advance directive, we suggest that institutions develop treatment policies for situations in which the wishes of patients who lack decisional capacity are not known. These policies should be designed to promote the patients' best interests, as defined by the consensus of the institutions' staff and members of the surrounding community.
Fifteen-Month Follow-up Study of Women Infected with<i>Chlamydia trachomatis</i>
Authors: William M. McCormack, Susan Alpert, Dorothy E. McComb, Roger L. Nichols, Deborah Z. Semine, Stephen H. Zinner
Journal: New England Journal of Medicine (1979)

AFTER many years during which they were of interest only to ophthalmologists and ornithologists, chlamydial infections recently have burst into general medical awareness.1 Hardly a month goes by without a report describing an etiologic role for Chlamydia trachomatis in yet another disease. It has now been shown that this interesting intracellular parasite is a cause of nongonococcal urethritis,2 infantile pneumonia,3 pelvic inflammatory disease4 and epididymitis,5 in addition to its long established role in trachoma, lymphogranuloma venereum and inclusion conjunctivitis.Despite the increasingly obvious importance of these organisms, little is known of their prevalence among different population groups or about the . . .
Postoperative Complications in Neurosurgical Practice: Recognition, Prevention, and Management
Authors: Charles B. Wilson
Journal: JAMA (1967)

The restrictive title hardly prepares the reader for an encyclopedia of operative neurosurgery. The authors, practicing neurosurgeons, take<i>complication</i>to mean therapeutic failure in the broadest sense. Accordingly, this book deals with the incidence and causes of neurosurgical failures, and does so exceedingly well. The longest of 12 chapters pertains to brain tumors. Following an introductory section on operative and postoperative problems in general, surgical aspects of individual tumors are discussed in detail. Astrocytomas of the cerebral hemisphere, third ventricle, and pons, having particular complications related to their locations, receive separate attention. In the section on acoustic neurinomas, complications are grouped logically into four periods: during surgery and immediate, intermediate, and late periods after surgery. Under pituitary adenomas the authors discuss six causes of death and eight nonfatal complications including recurrence. Other tumors are treated in proportion to their clinical importance. The chapter dealing with aneurysms contains detailed
Termination of paroxysmal supraventricular tachycardia by tecadenoson (CVT-510),a novel A1-adenosine receptor agonist
Authors: Eric N Prystowsky, Imran Niazi, Anne B Curtis, David J Wilber, Tristram Bahnson, Kenneth Ellenbogen, Anwer Dhala, Daniel M Bloomfield, Michael Gold, Alan Kadish, Richard I Fogel, Mario D Gonzalez, Luiz Belardinelli, Revati Shreeniwas, Andrew A Wolff
Journal: Journal of the American College of Cardiology (2003)
The Maximising STI Control (MSTIC) webtool: a new approach to facilitate the planning of services for sexually transmitted infections to maximise public health benefit
Authors: Catherine H Mercer, Neil Macdonald, Mark D F Shirley, Catherine R H Aicken, Claudia S Estcourt, Frances Keane, M Gary Brook, Peter J White, Jackie A Cassell
Journal: The Lancet (2013)
Differential effects of captopril and enalapril on tissue renin-angiotensin systems in experimental heart failure.
Authors: A T Hirsch, C E Talsness, A D Smith, H Schunkert, J R Ingelfinger, V J Dzau
Journal: Circulation (1992)

BACKGROUND Angiotensin converting enzyme (ACE) inhibitor therapy elicits beneficial responses from patients with heart failure. We hypothesized that a major site of action of these drugs is tissue ACE and that ACE inhibitors might differ in their ability to inhibit tissue ACE. To test this hypothesis, we assessed the effects of captopril and enalapril on blood pressure and renal function and on serum and tissue ACE activities in sham-operated rats and rats with heart failure induced by coronary artery ligation. METHODS AND RESULTS During short-term (1-week) treatment, captopril (200 mg.kg-1.day-1) and enalapril (25 mg.kg-1.day-1) elicited equipotent effects on blood pressure and inhibition of serum ACE activity (85%). The effects of long-term treatment (47 days) were then studied beginning 45 +/- 5 days after coronary ligation in four treatment groups: sham-operated, vehicle (n = 14); heart failure, vehicle (n = 10); heart failure, captopril (n = 8); and heart failure, enalapril rats (n = 7). During long-term treatment, captopril and enalapril caused comparable falls of 12-18 mm Hg in blood pressure (p &lt; 0.01 compared with vehicle treatment). There was no change in urine volume or sodium or potassium excretion in vehicle- or captopril-treated heart failure rats; in contrast, enalapril-treated heart failure rats demonstrated 83% and 10% increases in urine volume and daily sodium excretion, respectively, compared with vehicle-treated rats (both p &lt; or = 0.01). No significant changes in blood urea nitrogen or creatinine were observed with either treatment. Enalapril but not captopril elicited a significant decrease in serum and lung ACE activities. Captopril but not enalapril inhibited aortic ACE activity. Both agents caused a comparable inhibition of renal ACE activity. The magnitude of inhibition of renal ACE activity but not serum and vascular (aortic) ACE activities correlated with the long-term blood pressure response. Enalapril but not captopril normalized renal angiotensinogen expression; the magnitude of this effect correlated with the increase in daily urinary sodium excretion (r = -0.43; p &lt; or = 0.005). CONCLUSIONS These data suggest that chronic treatment with these two agents elicits differential effects on tissue ACE activities and renal angiotensinogen regulation. The differential renal effects of these agents may be important in the treatment of heart failure.
Modulation of experimental alcohol-induced liver disease by cytochrome P450 2E1 inhibitors
Authors: Michio Morimoto, Ann-Louise Hagbjörk, Yu-Jui Yvonne Wan, Paul C. Fu, Paolo Clot, Emanuele Albano, Magnus Ingelman-Sundberg, Samuel W. French
Journal: Hepatology (1995)

This study was done to determine if a relationship exists between CYP2E1 induction by ethanol, lipid peroxidation, and liver pathology in experimental alcohol-induced liver disease in the rat. Rats were fed ethanol with or without diallyl sulfide (DAS) or phenethyl isothiocyanate (PIC) intragastrically for 1 month. CYP2E1 induction by ethanol was correlated with lipid peroxidation, liver microsomal CYP2E1 hydroxylation of paranitrophenol, and the liver pathology score using the data from the PIC-fed rats. Some of the data from the ethanol and DAS-fed rats were not included here because they have been reported elsewhere. Microsomal CYP2E1 protein levels induction by ethanol was decreased by PIC ingestion. Similarly, PIC reduced the increase microsomal reduced form of nicotinamide-adenine dinucleotide (NADPH)-dependent lipid peroxidation and p-nitrophenol hydroxylase (PNPH) activity, induced by ethanol feeding. The lipid peroxidation was reduced to below control levels; however, the pathology score was partially but not significantly reduced by isothiocyanate feeding. CYP2E1 messenger RNA (mRNA) was decreased by both inhibitors of CYP2E1. Immunohistochemical staining of liver for CYP2E1 protein showed that the lobular distribution of the isozyme changed from the centrilobular to a diffuse pattern, with an increase in the periportal region when the CYP2E1 inhibitors were fed with ethanol, and that this change correlated with the change in the distribution of fat in the lobule. The data support the idea that there is a link between CYP2E1 induction by ethanol and the early phase of ethanol-induced liver injury in this rat model. This link may involve lipid peroxidation, but other factors related to CYP2E1 induction must also be involved.