tbuckley/cabot-search huggingface dataset:
INDUCTION OF IMMUNITY AND TOLERANCE IN VITRO BY HAPTEN PROTEIN CONJUGATES
Authors: Marc Feldmann
Journal: The Journal of Experimental Medicine (1972)

The capacity of dissociated spleen cell suspensions to be immunized by dinitrophenylated polymeric flagellin (DNP POL), in the absence of thymus-dependent lymphocytes or macrophages, provided a simple experimental system to investigate the mechanism of binding of antigen molecules to nonthymus-dependent lymphocyte (B cell) receptors during the induction of immunity or tolerance. Various nonimmunogenic DNP compounds were used to inhibit the anti-DNP response to DNP POL. By performing inhibition experiments of brief duration at 4°C, it was established that the inhibition of the anti-DNP response by nonimmunogenic compounds was due to competitive blockade of receptors, and not tolerance or receptor modulation. It was found that univalent DNP compounds were much less efficient inhibitors of the antibody response than multivalent DNP conjugates. The difference in inhibitory capacity between univalent and multivalent DNP human globulin (DNP HgG) suggested the importance of interaction with both combining sites of a single receptor antibody molecule. Nonimmunogenic highly conjugated DNP3POL was a more efficient inhibitor of the anti-DNP response to immunogenic DNP1POL than DNP12HgG, indicating that interactions at more than one receptor molecule are involved in immunization of B cells. Recent demonstrations of the rapid metabolic turnover of receptor antibody molecules suggests that the requirement for multipoint binding (to different receptors) may simply be to maintain the antigen at the cell surface in a dynamic system. Competitive inhibition experiments were also performed to investigate the mechanism of binding of DNP3POL in the induction of B cell tolerance. It was found that monovalent DNP compounds or multivalent DNP12HgG did not prevent the induction of tolerance, unlike their capacity to inhibit immunity, suggesting that a tolerance-inducing antigen binds more avidly to the cell membrane than an immunogen. The inhibition data obtained here, together with prior results describing the differential immunogenicity of DNP conjugates of different structure, and the importance of epitope density on DNP POL conjugates, permit certain conclusions about the details of antigen-receptor interaction in immunity and tolerance. Distinctions between the mechanisms of immune and tolerance induction are discussed.
461. Evaluation of In Vivo Model Systems for Safety Assessment of HIV-1 Based Lentiviral Vectors
Authors: Yuan Zhao, Selina Azam, Kenneth Keating, Robin Thorpe
Journal: Molecular Therapy (2006)

Vectors based on Lentiviruses are efficient gene-delivery vehicles as they are able to integrate into host genome and facilitate long-term transgene expression. There are increasing interests and significant progresses in the modification and the clinical applications of Lentiviral vectors. However, recent incidences of T-cell leukaemia in the X-SCID children receiving retroviral gene therapy reveal certain discrepancy among the pre-clinical and clinical studies. Divergent results on the potential oncogenic activity of Lentiviral vectors obtained from different model systems further raise consideration on the relevance and sensitivity of preclinical systems used for assessing their safety profile. Development of reliable testing systems for such purpose becomes increasingly important in the context of future safety control of lentiviral vectors. We reason that by evaluating gene responses to vector transduction in different in vivo models may provide us with comparative information on the sensitivity and suitability of available preclinical models and early indications of the potential adverse effects of these vectors. For this, we used cDNA microarray methodology to examine cellular gene changes in BALB/c and CD-1 mice, the two common murine models used in pharmacological and toxicological studies. Our results revealed a significant difference in the transcriptional responses to vector transduction between the two representative murine models tested. Modest gene changes, in terms of gene numbers and expression of oncogenes were observed in BALB/c mice, whereby over-expression of 15 oncogenes was detected in CD-1mice. We focused our interest in the expression of oncogenes, e.g. N-myc, A-Raf, Fli-1, Wnt-2b, and c-mer and c-jun in CD-1mice and further confirmed the over-expression of these genes using semi-quantitative RT-PCR. Distinctive effects of Lentiviral vectors on two murine models should be considered in the context of future development of sensitive assays for quality control of these vectors. Implication of oncogene expression in CD-1 mice requires further investigation.
Trends in Care by Nonphysician Clinicians in the United States
Authors: Benjamin G. Druss, Steven C. Marcus, Mark Olfson, Terri Tanielian, Harold Alan Pincus
Journal: New England Journal of Medicine (2003)

The 1990s saw rising numbers of graduates of training programs for nonphysician clinicians, passage of legislation expanding their scope of practice, and a proliferation of managed-care models that emphasized the use of these providers as a strategy for containing health care costs.We used two nationally representative surveys to examine trends in outpatient care provided by physicians and nonphysician clinicians between 1987 and 1997, adjusting for the case mix. Analyses examined care provided by 10 categories of nonphysician clinicians: chiropractors, midwives, nurses or nurse practitioners, optometrists, podiatrists, physician assistants, physical or occupational therapists, psychologists, social workers, and others.Between 1987 and 1997, the proportion of patients who saw a nonphysician clinician rose from 30.6 percent to 36.1 percent (adjusted relative risk for 1997 as compared with 1987, 1.42 [95 percent confidence interval, 1.35 to 1.50]). The trend was driven by an increase in the proportion of persons who visited both a physician and a nonphysician clinician (from 23.5 percent to 30.9 percent; adjusted relative risk, 1.49 [95 percent confidence interval, 1.40 to 1.58]), rather than an increase in the proportion who saw only a nonphysician clinician (from 7.2 percent to 5.3 percent; adjusted relative risk, 0.81 [95 percent confidence interval, 0.70 to 0.93]). This pattern was consistent in analyses of specific medical conditions and specific types of nonphysician clinicians. There was an increase in the proportion of patients obtaining preventive services from nonphysician clinicians and a decline in the proportion receiving acute care services from such clinicians.From 1987 to 1997, there was a degree of differentiation between physicians and nonphysician clinicians with respect to the services they provided but not with respect to the patients they treated. The implications of these findings hinge on the degree to which the increase in conjoint service delivery represents growing coordination or fragmentation of care.
Ratio of Free to Total Prostate-Specific Antigen in Patients with Prostatic Intraepithelial Neoplasia
Authors: Sahir Kili&ccedil;, Erdal Kukul, Ahmet Dani&scedil;man, Erol G&uuml;ntekin, Metin Sev&uuml;k
Journal: European Urology (1998)
SOME REMARKS ON THE RELIEF OF REMOTE NEUROSES, BY THE RESTORATION OF OCULAR EQUILIBRIUM.
Authors: FRANK ALLPORT
Journal: JAMA (1890)

The subject of ocular insufficiencies and oversufficiencies appears to be one of those crazes that occasionally strike the medical profession with cyclonic force. Like cyclones, these crazes are unexpected in their attacks and frightfully devastating while they last. Their careers are shortlived, but they leave many aching hearts behind to tell the story of over-credulous patients and over-zealous physicians. We can learn but little, it is true, without experimentation, but in the name of suffering humanity, there should be some limit placed, beyond which the pitiless drug or knife of the medical man may not leave its mark. What a multitude of mistakes must be laid to the demon of "reflex" action, who, like a fitful spirit, flits hither and thither in our human anatomy, and ever and anon lays his icy hand upon some one of our organs and claims it for his own. How quickly the
P238 The Effect Of Inhalation Duration On Lung Deposition With A Pressurised Metered-dose Inhaler (pmdi)
Authors: C. Van Holsbeke, J. Marshall, J. De Backer, W. Vos
Journal: Thorax (2014)

<h3>Rationale</h3> Although the guidance for using a pMDI is to inhale 'slow and deeply', many patients inhale fast over a short duration. The ERS/ISAM Task Force suggested 'slowly' equates to inhaling over 4–5 seconds (s) for adults1, a much clearer instruction. This study therefore examined the influence of inhalation time on total lung deposition (TLD) using Functional Respiratory Imaging (FRI). <h3>Methods</h3> Three-dimensional airway models of 6 asthma patients (mean FEV1 83%), treated with an ICS/LABA combination, were included. The lung deposition characteristics of an HFA-based pMDI (MMAD ~3.0μm; fine particle fraction (FPF) ~40%) were assessed using FRI. Simulations were performed on 3 different inhalation profiles matched for the same inspiratory volume (3 L) with durations of 1s, 3s and 5s and actuation at start of inhalation. <h3>Results</h3> For the 1s, 3s and 5s profiles, the TLD values were 22.81 ± 3.71%, 36.13 ± 2.51% and 41.61 ± 3.11% of nominal dose respectively, and were predicted using a concave down quadratic model (R2 = 0.87, p &lt; 0.001). The central to peripheral deposition ratios were 1.58, 0.81 and 0.57 respectively. <h3>Conclusions</h3> A 5 s inhalation led to highest TLD with greatest peripheral deposition. Increased deposition with longer times mainly reflected increased peripheral deposition, central deposition was less affected by flow rate. These data support ERS/ISAM guidance for inhaling over 4–5 sec to optimise deposition, although similar TLD were achieved with 3s. These data also suggest that high FPF pMDIs can achieve reasonable deposition even with short, fast inhalations. <h3>References</h3> Laube BL, <i>et al</i>. ERJ 2011;37(6):1308–417 Disclaimer acknowledgement: Reproduced with permission of the European Respiratory Society: Eur Resp J September 2014; 44, Suppl. 58: In Press
Nikolsky sign on cervix uteri in pemphigus
Authors: F. SAGHER, B. BERCOVICI, R. ROMEM
Journal: British Journal of Dermatology (2006)

Women suffering from pemphigus or from benign mucous membrane pemphigoid were examined gynaecologically. In thirteen of sixteen in whom the test was carried out, Nikolsky's was positive on the cervix uteri. It was consistently negative in control subjects.
LONG TERM EFFICACY OF AXILLARY VEIN APPROACH COMPARED WITH SUBCLAVIAN VEIN APPROACH FOR PERMANENT PACEMAKER IMPLANTATION
Authors: Ki Hun Kim, Kee-Joon Choi, Kyoung-Min Park, HyungOh Choi, Gi-Byoung Nam, You-Ho Kim, Dae-Kyeong Kim, Minkyung Oh, Pil-Sang Song, Dong-Kie Kim, Sang-Hoon Seol, Doo-IL Kim
Journal: Journal of the American College of Cardiology (2013)
Infarction of the Small Bowel
Authors: David Frajndlich, Richard L. Taylor
Journal: JAMA (1964)

ACUTE INFARCTION of the small bowel is a major abdominal problem; it is difficult to diagnose early and is often fatal despite treatment. It may be suspected following abdominal surgery, mesenteric vessel trauma, shock, congestive heart failure, chronic cardiac arrhythmia, or aortic insufficiency. However, diagnosis and treatment have been improving; occasional successful surgical restoration of the gastrointestinal circulation has been accomplished. The use of heparin sodium in massive doses is a new approach in cases diagnosed early. <h3>Report of a Case</h3> A 54-year-old male was admitted to the hospital complaining of severe abdominal pain and vomiting. Pain had started about six hours before admission, was colicky at first, then shifted to the lower right quadrant of the abdomen and became constant. A diagnosis of acute appendicitis was made. The patient had been discharged from the hospital a month before this admission with a diagnosis of congestive heart failure due to
Bulletin campaigns against withdrawal of Mixtard 30
Authors: N. Hawkes
Journal: BMJ (2010)

A campaign has been launched against the decision by the Danish drug company Novo Nordisk to withdraw a form of insulin used by 90 000 patients in the United Kingdom.

Mixtard 30, which is a 30:70 mixture of short acting and intermediate acting human insulin, is to be withdrawn from the market at the end of the year. Novo Nordisk’s decision, announced in June, caused disquiet among doctors and diabetes charities. Douglas Smallwood, chief executive of Diabetes UK, said at the time that he was “very disappointed” by the announcement and had sought unsuccessfully to have it reversed.

Ike Iheanacho, editor of the Drug and Therapeutics Bulletin (a BMJ Group publication), said that …
Bursts of non-deglutitive simultaneous contractions may be a normal oesophageal motility pattern.
Authors: J Janssens, V Annese, G Vantrappen
Journal: Gut (1993)

The frequency and characteristics of non-deglutitive motor activity of the human oesophagus and its relation to motility patterns in the antrum and upper small intestine were studied in 25 fasted healthy subjects. Motility of the oesophagus, antrum, and upper small intestine was recorded by means of a manometric perfused catheter system. The most striking non-deglutitive motility pattern consisted of repetitive bursts of non-sequential pressure peaks occurring in the smooth muscle portion of the oesophagus. The mean number of pressure peaks per burst was 2.7 (SD 2) waves with a mean amplitude of 19.5 (SD 9.9) mm Hg and a duration of 3.09 (SD 0.22) seconds. The highest amplitude was 80 mm Hg and the longest burst consisted of 13 repetitive waves. The bursts were recorded up to a distance of 15-20 cm above the lower oesophageal sphincter. Ninety five per cent of the bursts occurred during a 15 minute period before the onset of phase 3 of the migrating motor complex in the antral or upper small intestinal area, or during the lower oesophageal sphincter component of the migrating motor complex. In conclusion, spontaneous bursts of non-sequential pressure peaks occurred in the smooth muscle part of the human oesophagus in relation to phase 3 of the migrating motor complex. They represent the oesophageal body component of phase 3 of the migrating motor complex and are not a sign of oesophageal motor abnormalities.
Infusion of tumor necrosis factor/cachectin promotes muscle catabolism in the rat. A synergistic effect with interleukin 1.
Authors: E A Flores, B R Bistrian, J J Pomposelli, C A Dinarello, G L Blackburn, N W Istfan
Journal: Journal of Clinical Investigation (1989)

To improve our understanding of the metabolic role of cytokines in protein wasting, we estimated the rates of protein synthesis and degradation in muscle and liver tissues in intact rats treated with several doses of recombinant IL 1 and/or tumor necrosis factor (TNF)/cachectin. Protein breakdown in muscle and liver were derived in vivo from the relationship between [14C]leucine distribution and tissue dilution in reference to circulating leucine. Synthesis was derived from the relationship between [14C]leucine appearance in the protein-bound and free-tissue leucine pools. To specifically relate changes in leucine tracer metabolism to protein dynamics, we separately measured the effect of these cytokines on blood flow to different tissues. The increase in dilution of the tissue-free [14C]leucine by TNF and TNF/IL 1 mixture, but not by IL 1 alone, could not be explained by a hemodynamic effect of these cytokines. Rather, this finding indicated that muscle proteolysis is enhanced by TNF and synergistically augmented by the addition of IL 1. Compatible with these data was the finding that more prolonged infusions of recombinant TNF/cachectin and the combination with IL 1 increased urinary nitrogen excretion. Changes in [14C]leucine dilution in the liver were less pronounced than those in skeletal muscle and consistent with net anabolic effect of TNF on liver protein. We conclude that rats exposed systemically to sublethal doses of TNF respond with increasing muscle and decreasing liver proteolysis, similar to that observed in inflammation and in cancer.
Intramural and Pericapillary Distribution of Lipids in Gingival Tissue of Patients with Carbohydrate-Induced Hyperglyceridemia
Authors: JOHN L. CORNOG, WILLIAM T. FITTS, PETER T. KUO
Journal: Circulation (1968)

Gingival biopsy was performed on 16 patients with carbohydrate-induced hyperglyceridemia, in the attempt to discover histological abnormalities in the capillaries. For comparison, similar studies were also made on four patients with essential familial hypercholesteremia, on five whose hyperglyceridemia had been kept under control by a low carbohydrate diet for 6 to 26 months, and on eight healthy, normolipemic subjects. Variable amounts of Oil Red O-stainable lipid material were demonstrated both in and around the capillary wall in 13 of the 16 untreated hyperglyceridemic patients. Little or no such lipid-staining material was demonstrated in the biopsy material obtained from the remaining groups of subjects so studied. Microangiopathy of the pre-diabetic and diabetic type characterized by capillary basement membrane thickening was not demonstrated in any of the hyperlipemic patients in this series. Evidence is presented to support the concept that a sustained chylomicronemia is the primary factor in the production of the intramural and pericapillary collection of Oil Red O-staining lipids in these hyperglyceridemic patients.
Thyrotoxic Hypercalcemia, Renal Tubular Acidosis, and Pancreatitis
Authors: James M. Falko, Harold K. Berenzweig
Journal: Annals of Internal Medicine (1976)

Comments1 September 1976Thyrotoxic Hypercalcemia, Renal Tubular Acidosis, and PancreatitisJAMES M. FALKO, HAROLD K. BERENZWEIGJAMES M. FALKOSearch for more papers by this author, HAROLD K. BERENZWEIGSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-85-3-404_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the paper "Thyrotoxicosis Associated with Renal Tubular Acidosis and Acute Pancreatitis: A Case Report" published in the May issue (Ann Intern Med 84:569-570, 1976), numerous important points are omitted. There is no mention of the patient's lipid levels, history of alcohol or drug intake, or family history. A calcium level of 11.9 mg/ml in the face of pancreatitis is most unusual unless the patient has coexistent hyper-parathyroidism. Furthermore no autopsy description of the parathyroid glands was given. We believe that the author's hypothesis that the hyperthyroidism induced the hyper-calcemia, which then caused the pancreatitis, lacks adequate supporting...Reference1. BAXTERBONDY JP: Hypercalcemia of thyrotoxicosis. Ann Intern Med 65:429-442, 1966 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1976Volume 85, Issue 3Page: 404-404KeywordsAcute pancreatitisAlcoholsAutopsyCalciumDrugsHypercalcemiaHyperthyroidismLipidsPancreatitisParathyroid Issue Published: 1 September 1976 PDF DownloadLoading ...
Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon α-2a (40 kd)/ribavirin therapy
Authors: Donald M. Jensen, Timothy R. Morgan, Patrick Marcellin, Paul J. Pockros, Rajender K. Reddy, Stephanos J. Hadziyannis, Peter Ferenci, Andrew M. Ackrill, Bernard Willems
Journal: Hepatology (2006)

Approximately one third of hepatitis C virus (HCV) genotype 1 patients achieved a sustained virological response (SVR) after 24 weeks of treatment with peginterferon α-2a (40 kd) plus ribavirin in a randomized, multinational trial. We aimed to identify factors associated with a rapid virological response (RVR) at week 4 (HCV RNA &lt;50 IU/mL) and a SVR (HCV RNA &lt;50 IU/mL at the end of follow-up) in these patients. Stepwise multiple logistic regression analysis was used to explore the prognostic factors for a RVR and SVR in genotype 1 patients treated for 24 weeks. Fifty-one of 216 (24%) genotype 1 patients in the 24-week treatment groups had a RVR. SVR rates were considerably higher in patients with than without a RVR (89% vs. 19%, respectively). Patients with a baseline HCV RNA of less than 200,000 IU/mL (OR 9.7, 95% CI 4.2-22.5; P &lt; .0001) or 200,000-600,000 IU/mL (OR 3.6, 95% CI 1.5-9.1; P = .0057) were more likely to achieve a RVR than those with HCV RNA greater than 600,000 IU/mL. HCV subtype (1b vs. 1a) was also independently associated with RVR (OR 1.8, 95% CI 0.9-3.7; P = .0954). RVR (OR 23.7 vs. no RVR, 95% CI 9.1-61.7) and baseline HCV RNA less than 200,000 IU/mL (OR 2.7 vs. &gt;600,000 IU/mL, 95% CI 1.1-6.3; P &lt; .026) were significant and independent predictors of SVR in patients treated for 24 weeks. In conclusion , patients infected with HCV genotype 1 and treated with peginterferon α-2a/ribavirin sustained a RVR 24% of the time. This portends an 89% probability of a SVR after 24 weeks of treatment. (Hepatology 2006;43:954–960.)
Damage Prevention and Control for Financial Incapacity
Authors: Charles P Sabatino
Journal: JAMA (2011)

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