tbuckley/cabot-search huggingface dataset:
Hepatitis C virus-related proteins in kidney tissue from hepatitis C virus-infected patients with cryoglobulinemic membranoproliferative glomerulonephritis
Authors: D Sansonno, L Gesualdo, C Manno, F P Schena, F Dammacco
Journal: Hepatology (1997)

Membranoproliferative glomerulonephritis (MPGN) may be a component of a generalized vasculitis as well as a component of the clinical expression of type-II mixed cryoglobulinemia (MC). Several studies have established a striking association between hepatitis C virus (HCV) infection and MC. The potential role of HCV in the pathogenesis of MPGN, which occurs in almost half of the cases of MC patients, has not been fully investigated, and the demonstration of HCV proteins as the antigenic constituent of the glomerular immune deposits has remained elusive. Kidney biopsy specimens were obtained from 12 HCV RNA, antibody to HCV (anti-HCV)-positive patients with MPGN and type-II MC, and from 8 controls (3 HCV RNA, anti-HCV-negative patients with MPGN and MC and 5 with noncryoglobulinemic “idiopathic” MPGN). Murine monoclonal antibodies developed against c22-3, E2/NS1, c33c, c100-3, and NS5 proteins were used to detect HCV-related antigens by indirect immunohistochemistry. Acid electroelution of tissue sections was performed to enhance the sensitivity of the immunohistochemical method. Specific HCV-related proteins were detected in glomerular and tubulo-interstitial vascular structures in 8 (66.7%) HCV-positive MC patients and in none of the HCV RNA, anti-HCV-negative controls. HCV immunoreactive deposits displayed the following two major patterns: 1) a linear, homogeneous deposition along glomerular capillary walls, including endothelial cells and sub-endothelial spaces; and 2) a granular bead-like appearance with distinct deposits in mesangial and paramesangial cells. Immunoglobulin G (IgG) and M (IgM) and C3 fraction deposition in adjacent kidney sections displayed features comparable with those found for HCV deposits. Patients with granular deposits showed more pronounced renal impairment and severe proteinuria. These findings indicate that in MC patients with HCV-associated MPGN, kidney deposits consist of HCV-containing immune complexes that are likely to play a direct pathogenetic role in the renal damage.
NMR structure of phospho-tyrosine signaling complexes
Authors: Carol Beth Post, Beverly S. Gaul, Elan Zohar Eisenmesser, Michael L. Schneider
Journal: Medicinal Research Reviews (1999)

A structural basis for activation and substrate specificity of src tyrosine kinases, and regulation of protein–protein association by tyrosine phosphorylation is described. Lyn, a src-family tyrosine kinase, recognizes and phosphorylates the immunoreceptor tyrosine-based activation motif, ITAM, a critical component in transmembrane signal transduction in hemopoietic cells. The structure of an ITAM peptide substrate bound to an active form of Lyn tyrosine kinase was determined by high-resolution NMR, and a model of the complex was generated using the crystallographic structure of Lck, a closely related Src-family kinase. The results provide a rationale for the conserved ITAM residues and specificity of Lyn, and suggest that substrate plays a role in stabilizing the kinase conformation optimal for catalysis. It is our hope that the Lck-ITAM peptide model complex will be useful in aiding structure-based drug design efforts that target substrate binding determinants in the design. Concerning the regulation of protein–protein association, we report on a complex between erythrocyte band 3 and two glycolytic enzymes, aldolase and glyceraldehyde-3-phosphate dehydrogenase. The formation of this complex is negatively regulated by tyrosine phosphorylation of band 3 by p72syk tyrosine kinase. In red blood cells, this association results in a decrease in glycolysis due to competitive inhibition of the glycolytic enzymes. The structure of band 3 recognized by the glycolytic enzymes was determined by solution NMR, and found to be a loop structure with tyrosine centrally positioned and excluded from intermolecular contact. This phosphorylation sensitive interaction, or PSI, loop may be the basis of a general mechanism for negative regulation through tyrosine phosphorylation. © 1999 John Wiley & Sons, Inc. Med Res Rev, 19, No. 4, 295–305, 1999.
The Clinical Pharmacist as a Specialist
Authors: KIM L. KELLY
Journal: Annals of Internal Medicine (1980)

Letters1 July 1980The Clinical Pharmacist as a SpecialistKIM L. KELLY, PHARM.D.KIM L. KELLY, PHARM.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-1-153_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The editorial by Drs. Brater and Pettinger (1) that accompanied the article on generic prescribing by Francetíc and coworkers (2) seems to digress from the generic prescribing issue to a discussion of the clinical pharmacist. The relationship of the education and training of clinical pharmacists to the performance of community pharmacists in generic substitution situations in Rochester, New York, is not readily apparent.The clinical pharmacist is in most cases a specialist. He or she generally possesses the doctorate degree in pharmacy (Pharm. D.), and also commonly has had residency training. In addition to substantial emphasis on...References1. BRATERPETTINGER DW. The generic prescribing issue. Ann Intern Med. 1980;92:426-7. Editorial. LinkGoogle Scholar2. FRANCETÍCLASAGNAWEINTRAUBKARCH ILMF. Prescription prices under the New York generic substitution law. Ann Intern Med. 1980;92:419-23. LinkGoogle Scholar3. . Abstracts for papers—eighty-first annual meeting. Clin Pharmacol Ther. 1980;27:243-96. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: American College of Clinical Pharmacy Kansas City, MO 64108 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1980Volume 93, Issue 1_Part_1Page: 153-154KeywordsPharmacistsResidency Issue Published: 1 July 1980 PDF DownloadLoading ...
Proteasomal Processing of Albumin by Renal Dendritic Cells Generates Antigenic Peptides
Authors: Daniela Macconi, Chiara Chiabrando, Silvia Schiarea, Sistiana Aiello, Linda Cassis, Elena Gagliardini, Marina Noris, Simona Buelli, Carla Zoja, Daniela Corna, Caterina Mele, Roberto Fanelli, Giuseppe Remuzzi, Ariela Benigni
Journal: Journal of the American Society of Nephrology (2008)

The role of dendritic cells (DC) that accumulate in the renal parenchyma of non-immune-mediated proteinuric nephropathies is not well understood. Under certain circumstances, DC capture immunologically ignored antigens, including self-antigens, and present them within MHC class I, initiating an autoimmune response. We studied whether DC could generate antigenic peptides from the self-protein albumin. Exposure of rat proximal tubular cells to autologous albumin resulted in its proteolytic cleavage to form an N-terminal 24-amino acid peptide (ALB1-24). This peptide was further processed by the DC proteasome into antigenic peptides that had binding motifs for MHC class I and were capable of activating syngeneic CD8+ T cells. In vivo, the rat five-sixths nephrectomy model allowed the localization and activation of renal DC. Accumulation of DC in the renal parenchyma peaked 1 wk after surgery and decreased at 4 wk, concomitant with their appearance in the renal draining lymph nodes. DC from renal lymph nodes, loaded with ALB1-24, activated syngeneic CD8+ T cells in primary culture. The response of CD8+ T cells of five-sixths nephrectomized rats was amplified with secondary stimulation. In contrast, DC from renal lymph nodes of five-sixths nephrectomized rats treated with the proteasomal inhibitor bortezomib lost their capacity to stimulate CD8+ T cells in primary and secondary cultures. These data suggest that albumin can be a source of potentially antigenic peptides upon renal injury and that renal DC play a role in processing self-proteins through a proteasome-dependent pathway.
Case 43-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Frank C. Wheelock, Austin L. Vickery
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 75-year-old woman was admitted to the hospital because of abdominal pain and diarrhea.Twenty-five years previously there was the onset of intermittent diarrhea. Five years later sigmoidoscopic examination revealed discrete ulcerations of the sigmoid colon, and a barium-enema examination showed ulcerations that involved the transverse, descending and sigmoid colon. Stool cultures and repeated stool examinations for ova and parasites were negative. Oxytetracycline and sulfadiazine were given, with improvement. She was well thereafter except for recurrent episodes of depression. Repeated sigmoidoscopic examinations revealed no abnormality.Two years before admission stiffness and pain developed in multiple joints; atrial . . .
Surgical Implications of Sweating
Authors: Robert I. Lowenberg
Journal: JAMA (1963)

Sweating was induced in 56 patients for the purpose of predicting the results of lumbar sympathectomy. Nitrazine paper was applied to the skin as an indicator of the appearance of perspiration. The limb affected by vascular disease was then compared with the contralateral limb. A prediction formulated on the basis of this test was recorded before each of 68 sympathectomies performed in these patients, and the findings after operation were then compared. Among 41 nondiabetic patients, the good results that had been predicted in 39 cases, and the poor results predicted in two, were realized. Among 15 diabetic patients, however, there were five prediction-failures. If a patient with ischemic extremities is free from diabetes, the sweating test should help in planning the treatment.
Infections with<i>Eikenella corrodens</i>
Authors: GERALD J. DORFF
Journal: Annals of Internal Medicine (1974)

Eikenella corrodens is a facultative anaerobic Gram-negative bacillus of uncertain pathogenicity for man. Our interest in E. corrodens was stimulated by two patients with convincing infections with this organism; one was a case of meningitis and the other a fatal case of bacterial endocarditis. Accordingly, we reviewed the charts of 24 patients from whom E. corrodens had been isolated from clinical specimens during a recent 6-month period at one hospital. Eight of these patients were considered to have clinically significant infections with this organism because it was either the only pathogen isolated or was isolated from clinical specimens that were believed to be free from contamination. Seven of the eight patients had abdominal abscesses, and one had an empyema. Advanced age, ruptured viscus, and underlying carcinoma seemed to predispose to infection with E. corrodens. The mortality rate was 30% even though the organism seems to be sensitive to most of the commonly used antibiotics. The pathogenic potential of E. corrodens can no longer be doubted. It should be sought more often as a possible causal agent of infection.
An Early Appointment to Outpatient Cardiac Rehabilitation at Hospital Discharge Improves Attendance at Orientation
Authors: Quinn R. Pack, Mouhamad Mansour, Joaquim S. Barboza, Brooks A. Hibner, Meredith G. Mahan, Jonathan K. Ehrman, Melissa A. Vanzant, John R. Schairer, Steven J. Keteyian
Journal: Circulation (2012)

Background— Outpatient cardiac rehabilitation (CR) decreases mortality rates but is underutilized. Current median time from hospital discharge to enrollment is 35 days. We hypothesized that an appointment within 10 days would improve attendance at CR orientation. Methods and Results— At hospital discharge, 148 patients with a nonsurgical qualifying diagnosis for CR were randomized to receive a CR orientation appointment either within 10 days (early) or at 35 days (standard). The primary end point was attendance at CR orientation. Secondary outcome measures were attendance at ≥1 exercise session, the total number of exercise sessions attended, completion of CR, and change in exercise training workload while in CR. Average age was 60±12 years; 56% of participants were male and 49% were black, with balanced baseline characteristics between groups. Median time (95% confidence interval) to orientation was 8.5 (7–13) versus 42 (35 to NA [not applicable]) days for the early and standard appointment groups, respectively ( P &lt;0.001). Attendance rates at the orientation session were 77% (57/74) versus 59% (44/74) in the early and standard appointment groups, respectively, which demonstrates a significant 18% absolute and 56% relative improvement (relative risk, 1.56; 95% confidence interval, 1.03–2.37; P =0.022). The number needed to treat was 5.7. There was no difference ( P &gt;0.05) in any of the secondary outcome measures, but statistical power for these end points was low. Safety analysis demonstrated no difference between groups in CR-related adverse events. Conclusions— Early appointments for CR significantly improve attendance at orientation. This simple technique could potentially increase initial CR participation nationwide. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01596036.
Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation
Authors: Peter W. Collins, Sybil Hirsch, Trevor P. Baglin, Gerard Dolan, John Hanley, Michael Makris, David M. Keeling, Ri Liesner, Simon A. Brown, Charles R. M. Hay
Journal: Blood (2006)
miR-155 expression is associated with chemoimmunotherapy outcome and is modulated by Bruton’s tyrosine kinase inhibition with Ibrutinib
Authors: D Guinn, A S Ruppert, K Maddocks, S Jaglowski, A Gordon, T S Lin, R Larson, G Marcucci, E Hertlein, J Woyach, A J Johnson, J C Byrd
Journal: Leukemia (2014)
Young Academic Physicians and Publication
Authors: Myron L. Lecklitner
Journal: JAMA (1986)

To the Editor.—  Dr Strasburger's commentary 1 concerning medical writing was both informative and entertaining. Unfortunately, virtually all of his major points were woefully true. However, we differ in our opinion regarding the requirement that young academic physicians publish. He recommends that this practice be terminated. I believe his recommendation to be self-defeating and counter to one of the main purposes for the existence of colleges of medicine: the generating and rapid dissemination of new ideas.  I do not envy younger physicians who are committing themselves to academic careers at this time. Vying for funds is much more competitive these days; from 1973 to 1983, applications to the National Institutes of Health have increased from 9,541 to 19,310. 2 In addition, primary care physicians are reluctant to raise their diagnosis-related group cost profiles by allowing their patients to enter clinical studies in which the cost of the study is passed
Marine???Lenhart Syndrome
Authors: B CHANDRAMOULY, D MANN, R P CUNNINGHAM, E GIEGERICH
Journal: Clinical Nuclear Medicine (1992)

The Marine–Lenhart Syndrome is a variant of Graves' disease with the following criteria: 1) the thyroid scan shows an enlarged gland and one or two poorly functioning nodules; 2) the nodule is thyroid-stimulating hormone (TSH) dependent and the paranodular tissue is TSH independent; 3) following endogenous or exogenous TSH stimulation, the return of function in the nodule can be demonstrated; and 4) the nodule is benign histologically.
Modernization: A Necessity for Hospitals
Authors: Jacob K. Javits
Journal: New England Journal of Medicine (1969)

IN an era of change, we must ask how much hospital care is changing — how it is affected by high costs. Is obsolescence seriously endangering the quality and quantity of care? How much can we modernize our hospitals?The public sees costs of patient care doubling and doubling again. These mounting charges are shared not only by the patient and his family but by the community and some 90 per cent of all Americans who have health-care insurance.The hospital administrator sees an ever increasing demand for facilities, increased expenses for more sophisticated equipment, rising hospital worker wages and . . .
Ethical Issues in Stem Cell Research
Authors: Bernard Lo, Lindsay Parham
Journal: Endocrine Reviews (2009)

Stem cell research offers great promise for understanding basic mechanisms of human development and differentiation, as well as the hope for new treatments for diseases such as diabetes, spinal cord injury, Parkinson’s disease, and myocardial infarction. However, human stem cell (hSC) research also raises sharp ethical and political controversies. The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood. The reprogramming of somatic cells to produce induced pluripotent stem cells avoids the ethical problems specific to embryonic stem cell research. In any hSC research, however, difficult dilemmas arise regarding sensitive downstream research, consent to donate materials for hSC research, early clinical trials of hSC therapies, and oversight of hSC research. These ethical and policy issues need to be discussed along with scientific challenges to ensure that stem cell research is carried out in an ethically appropriate manner. This article provides a critical analysis of these issues and how they are addressed in current policies.
Effect of Treatment of Thyrotoxicosis on Exophthalmos
Authors: W. R. Greig, S. A. Aboul-Khair, S. D. Mohamed, J. Crooks
Journal: BMJ (1965)

MEDICIsOURNAL 50928 days of onset of symptoms, were reported.Residual paralysis was found in only four cases of paralytic poliomyelitis occurring between 5 and 28 days after vaccination, an incidence of 1 in four and a half million doses administered.Three of the four were infants: there was no evidence, as in the United States, of a higher incidence in adults.No par- ticular vaccine batches were implicated.Studies of the age, sex, and geographical distribution of cases and of their vaccination histories did not reveal any important differences between vaccine-associated and other cases.It is considered unlikely that disease was caused by spread of vaccine virus to contacts of vaccinated persons.Type 3 poliovirus was isolated proportionately more often from vaccine-associated than from other cases, but this finding was not unexpected after administration of vaccine containing all three virus types.The frequency of isolation of poliovirus from other cases of paralytic poliomyelitis fell between 1962 and 1963-4, suggesting that a greater proportion of cases diagnosed as poliomyelitis in the later years may not have been due to infection with poliovirus.It is concluded that the risk, if any, of the vaccine causing serious disease was extremely small, and, in view of the benefits conferred by vaccination, it did not justify any change in the present recommendations for the use of oral (Sabin) vaccine.We are indebted to the many medical officers of health, hospital clinicians, general practitioners, and virologists who have co-operated in providing information concerning their patients, and to the Ministry of Health for the statistics on the use of oral vaccine.
Europe's plan to tighten regulation of devices will not reach US standards
Authors: R. Coombes
Journal: BMJ (2012)

Plans to tighten Europe’s regulation of medical devices in the wake of the recent breast implant scandal will not go as far as the stricter controls in operation in the United States, it emerged last week.

Instead, proposals to be put before the European parliament only partially tighten the regulatory grip on device manufacturers. The recent Poly Implant Prosthese (PIP) scandal, when an estimated 40 000 UK women were given breast implants filled with non-medical grade silicone, exposed key weaknesses in the European system.1 By contrast, the implants were never approved for use in the US.

Jacqueline Minor, director for consumer policy at the European Commission, said, “The PIP scandal was very salutary for us. It was a fraud, quite deliberate criminality, which you can never …
Community general practitioners
Authors: M. Cohen
Journal: BMJ (1984)

Case 3-A 20 year old man had been treated with penicillamine for severe intention tremor and dysarthria.He responded well but later stopped his medication and his symptoms recurred.Treatment was restarted using penicillamine and zinc sulphate.After two weeks there was no improvement and he had developed severe vomiting.Zinc was stopped and he recovered completely over six months on penicillamine alone.Case 4-A 14 year old girl presented with severe dystonia, frequent painful muscular spasms, dysarthria, and dysphagia.Penicillamine rapidly induced a severe thrombocytopenia and had to be stopped.She was -treated for a year with trientine with no appreciable clinical improvement although the blood and urine copper concentrations im- proved satisfactorily.At the end of a year zinc acetate, 84 mg (50 mol Zn + +) three times a day, was added to her treatment.She made a slow but significant improvement.After six months she was able to attend a school for the physically handicapped although she still used a wheelchair.No two patients with Wilson's disease are ever the same, either clinically or in their response to treatment.The reasons for this remain obscure.Zinc sulphate is not a panacea for the treatment of Wilson's disease but may be a valuable addition to the treatments now available.Careful evaluation in a large series would be helpful.