tbuckley/cabot-search huggingface dataset:
The Experimental Foundations of Modern Immunology.
Authors: William R. Clark
Journal: Annals of Internal Medicine (1983)

The Concept of Immunization Structure of the Immune System Resolution of the Basic Structure of Immunoglobulins The Properties and Fine Structure of Immunoglobulins Genetic Basis of Immunoglobulin Structure Structure - Function Relationships in Antibody Molecules Complement Historical Development of the Concept of Major Histocompatibility Gene Complexes Genetic Organization of the Major Histocompatibility Complexes of Mice and Humans Biochemistry and Molecular Genetics of Major Histocompatibility Gene Complexes Lymphocyte Subpopulations The Basic Biology of T Cells and B Cells The Humoral Immune Response Cell-Mediated Cytotoxicity The Role of the Thymus in Development of the T-Cell Receptor Repertoire Immunity to Infection Reactions of Immunological Injury: Hypersensitivity and Inflammation Autoimmunity Clinical Organ Transplantation Immunity and Cancer Index.
Studies of the Control of Plasma Aldosterone Concentration in Normal Man
Authors: Gordon H. Williams, Michael L. Tuck, Leslie I. Rose, Robert G. Dluhy, Richard H. Underwood
Journal: Journal of Clinical Investigation (1972)

The peripheral plasma levels of aldosterone, renin activity, potassium, sodium, corticosterone, and cortisol were measured in six normal subjects four times daily-10 a.m., 2 p.m., 5 p.m., 11 p.m.-on 3 consecutive days. A constant daytime activity program was maintained throughout the study. After 5 days on a 10 mEq sodium/100 mEq potassium isocaloric intake, the mean upright 10 a.m. plasma renin activity was 1773+/-186 ng/100 ml per 3 hr and the mean plasma aldosterone, 81+/-14 ng/100 ml. These two parameters fell continuously throughout the day parallel to the fall in plasma cortisol and corticosterone. In response to 2 liters of normal saline infused from 10 a.m. to 2 p.m. on 2 consecutive days, plasma aldosterone levels fell significantly to 13+/-5 ng/100 ml at 2 p.m. after the 1st day's infusion and to 6+/-1 ng/100 ml at 2 p.m. after the 2nd. Plasma renin activity demonstrated a parallel fall to 368+/-63 ng/100 ml per 3 hr and 189+/-27 ng/100 ml per 3 hr at 2 p.m. on the 1st and 2nd days, respectively. There was no significant alteration in plasma levels of cortisol, corticosterone, potassium, or sodium on the 2 days of sodium loading in comparison with the control day. In an additional study, five normal supine subjects received 500 ml saline/hr for 6 hr. As in the 2 day study, plasma aldosterone and renin activity had parallel decrements at 1, 2, 4, and 6 hr after the start of the saline infusion. From these studies, it is concluded that plasma renin activity is the dominant factor controlling plasma aldosterone when sodium-depleted normal subjects are acutely repleted.
Response prediction to a 5-Fluorouracil based first-line palliative chemotherapy for metastatic colorectal cancer by gene expression profiling of liver metastases using DNA microarrays
Authors: W. M. Brueckl, R. S. Croner, W. Hohenberger, M. Munnes, R. Wirtz, I. Zeittraeger, T. Meyer, T. Papadopoulos, E. G. Hahn, A. Wein
Journal: Journal of Clinical Oncology (2005)

3558 Background: An individualized tumor tailored chemotherapy will improve survival of patients with metastatic colorectal carcinoma. However, this aim requires reliable molecular markers, which will predict tumor response to a specific chemotherapy. Therefore, we analyzed gene expression profiles of liver metastases of patients with colorectal carcinoma before application of a palliative 5-Fluorouracil (5-FU) based chemotherapy. Methods: 30 samples of primary colorectal carcinoma and metastatic liver tissue were laser microdissected and the RNA was isolated, amplified according to the ‘Eberwine’ protocol and hybridized to Affymetrix HG U-133A microarrays. After surgery of the primary tumor all patients were treated within the framework of a palliative first-line phase III study containing a continuous infusion of 5-FU and folinic acid. Response to chemotherapy was verified by CT scans according to WHO criteria. Gene expression profiles were compared with response to chemotherapy. Results: By using statistical tests (T-Test, Welch, Wilcoxon Kolmogorov-Wilcoxon),support vector machine algorithms and principal component analysis 123 transcripts were identified to be informative with regard to response prediction. In cross validation experiments a 57-gene predictor was sufficient to correctly classify 29/30 (96.7%) of the samples. Among those genes discriminating responders from non-responders were rTS beta, AIF1, HOXD11 and PPARgamma. Results obtained by Affymetrix analysis correlated well with independent technical evaluation by using semi-quantitative RT-PCR. Moreover, the classifier was validated in an independent cohort of 8 subsequent patients. Conclusions: We have identified preliminary molecular profiles of liver metastases of patients with colorectal carcinomas that appear to predict response or lack of response to a 5-FU based chemotherapy. This technology, when validated, may reduce unnecessary treatment and toxicity in colorectal cancer patients not responding to 5-FU. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Health Care AG
Abstract 2887: Molecular farming and molecular engineering of cancer vaccines
Authors: Sourabh Shukla, Nicole F. Steinmetz
Journal: Cancer Research (2014)

Abstract Human epidermal growth factor receptor 2 (HER2)+ cancers are aggressive, have poor prognoses, high rate of metastasis and relapse. Immunotherapy (e.g. trastuzumab) has shown improvement in outcome for HER2+ patients. Development of drug resistance and short half-lives limiting the duration of the therapy, are barriers in the development of effective therapeutic strategies. Furthermore, while passive immunotherapy provides treatment, it does not reduce the risk of recurrence of the disease. Therefore, we propose a HER2 vaccine to mount an active HER2-specific immune response, with long lasting immunological memory to overcome the limitations of passive immunotherapy and prevent tumor progression, metastasis, and relapse. We hypothesize that integration of HER2 epitopes on the plant-produced vaccination platform potato virus X (PVX) will overcome immunological tolerance against HER2. We have shown that PVX naturally targets dendritic and B-cells stimulating Th1 biased immunity, important for successful tumor prevention. The carrier acts as an adjuvant, improves stability of epitopes, and increases circulation time, therefore ensuring a sustained stimulus post vaccination and production of HER2-specific antibodies that could act against HER2+ tumors via a variety of effector mechanisms. Immunizations of FBV/N mice resulted in the production of HER2-specific antibodies, as shown by ELISA and confocal microscopy using HER2+ human cancer cell lines. Vaccination studies using animals pre-disposed to HER2+ cancer are currently ongoing. Our long-term goal is to produce the vaccine through molecular farming in edible plant tissue and make it available globally, especially in underdeveloped countries where repeated administration of costly immunotherapies is not affordable or unavailable. Citation Format: Sourabh Shukla, Nicole F. Steinmetz. Molecular farming and molecular engineering of cancer vaccines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2887. doi:10.1158/1538-7445.AM2014-2887
Increased NF-κB and decreased HDAC2 expression in the skeletal muscle of mice exposure to cigarette smoke
Authors: Zhiyi He, Yili He, Jianquan Zhang, Qiuli Liang, Jing Bai, Guangnan Liu, Meihua Li, Xiaoning Zhong
Journal: European Respiratory Journal (2014)

To explore skeletal muscle inflammation and structural alterations in the gastrocnemius muscle of mice that have been chronically exposed to CS. The lung and skeletal muscle structures, IL-8 and TNF-α concentrations, and NF-κB and HDAC2 expression levels were investigated . Compared to the control group, mice developed emphysema abnormalities after 3 months of CS exposure. The IL-8, TNF-a, (Table 2) and NF-κB levels were increased in the CS-exposed mice (Figure 2), whereas the weight (Table 1) and HDAC2 levels were decreased (Figure 1).
Abstract 648: Semi-synthetic peptibodies are a novel personalized therapeutic with activity against lymphoma <i>in vitro</i> and <i>in vivo</i>
Authors: James Torchia, Patrick Ng, Homer Chen, Kipp Weiskopf, Ronald Levy
Journal: Cancer Research (2014)

Abstract The complementarity determining region, or idiotype, of the surface immunoglobulin receptor is a true tumor-specific marker on B-cell lymphomas unique to each patient. Antibodies against idiotype can induce complete regression of lymphoma in patients, but since this requires the generation of a custom monoclonal antibody for each patient, it has not been practical. We have developed a method for targeting idiotype using a novel construct that we refer to as a “semi-synthetic peptibody”. It consists of a synthetic peptide ligand for idiotype that is covalently linked to the amino terminus of a recombinant IgG Fc domain. Peptide ligands for idiotype can be identified by high throughput screens of random peptide libraries and produced inexpensively by solid-phase synthesis. Linkage of these idiotype ligands to the Fc domain enhances their pharmacokinetics and augments their anti-tumor effect by activating innate immune effectors. Since each patient-specific synthetic peptide can be chemically linked to a common IgG Fc domain, this modular design yields a custom therapeutic that may be more practical to produce than a unique biologic monoclonal antibody. We demonstrate that semi-synthetic peptibodies bind specifically to the idiotype of tumor cells and induce apoptosis by crosslinking surface immunoglobulin. Additionally, they trigger antibody dependent cellular cytotoxicity, antibody mediated phagocytosis, and complement-mediated lysis of opsonized lymphoma cells in vitro. They possess a favorable pharmacokinetic profile and are sufficient to clear tumor in SCID mice challenged intravenously with a luciferase-labeled human lymphoma cell line. Tumor clearance in vitro and in vivo mediated by peptibody was superior to that achievable with an anti-idiotype monoclonal antibody. Thus, semi-synthetic anti-idiotype peptibodies demonstrate multimodal activity against lymphoma cells in vitro and clear human lymphoma in a disseminated xenograft model. This modular, semi-synthetic design may enable a personalized and targeted therapy that is feasible to produce for patients with B-cell lymphoma. Citation Format: James Torchia, Patrick Ng, Homer Chen, Kipp Weiskopf, Ronald Levy. Semi-synthetic peptibodies are a novel personalized therapeutic with activity against lymphoma in vitro and in vivo. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 648. doi:10.1158/1538-7445.AM2014-648
CALCINOSIS TREATED BY PARATHYROIDECTOMY
Authors: Elmer C. Bartels, Richard B. Cattell
Journal: Annals of Internal Medicine (1942)

Case Reports1 November 1942CALCINOSIS TREATED BY PARATHYROIDECTOMYELMER C. BARTELS, M.D., F.A.C.P., RICHARD B. CATTELL, M.D.ELMER C. BARTELS, M.D., F.A.C.P.Search for more papers by this author, RICHARD B. CATTELL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-17-5-859 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSubcutaneous calcinosis, a disease tending to serious bodily disability, presents a most difficult therapeutic problem. It is usually the sequel to dermatomyositis or some inflammatory disease in the skin or subcutaneous tissue, and produces difficulty by interfering with proper skeletal function by restricting the movements of muscles and tendons. The circulation of the skin and surrounding tissues may be disturbed and, at times, ulceration and infection may take place in the region of the calcium deposits.Since the calcium deposits are usually considered to be fixed and the destruction of muscles and tendons irreparable, any type of treatment seems almost...Bibliography1. KENNEDY RL: Calcinosis. Presentation of a case, Proc. Staff Meet. Mayo Clin., 1932, vii, 329-330. Google Scholar2. RAMSDELL EG: Parathyroidectomy for calcinosis syndrome, Trans. Am. Assoc. for Study of Goiter, 1939, pp. 183-191. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ELMER C. BARTELS, M.D., F.A.C.P.; RICHARD B. CATTELL, M.D.Affiliations: Boston, Massachusetts*Received for publication December 4, 1941. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySOFT TISSUE CALCIFICATION, WITH SPECIAL REFERENCE TO ITS OCCURRENCE IN THE "COLLAGEN DISEASES"*CLAYTON E. WHEELER, ARTHUR C. CURTIS, F.A.C.P., EDWARD P. CAWLEY, ROBERT H. GREKIN, BERTRAM ZHEUTLINIdiopathic calcinosis circumscriptaEXTENSIVE INTERSTITIAL CALCINOSIS WITH OSTEOPOROSIS AND SCLERODERMA-DERMATOMYOSITIS 1 November 1942Volume 17, Issue 5 Page: 859-863 Keywords Calcium Dermatomyositis Disabilities Muscles Myositis Parathyroidectomy Skin diseases Skin infections Tendons Ulcers ePublished: 1 December 2008 Issue Published: 1 November 1942 PDF downloadLoading ...
CORTISONE TREATMENT OF OCULAR PALSY IN SARCOIDOSIS
Authors: I FREEMAN
Journal: Annals of Internal Medicine (1954)

Case Reports1 February 1954CORTISONE TREATMENT OF OCULAR PALSY IN SARCOIDOSISIRVING FREEMAN, M.D.IRVING FREEMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-40-2-356 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe occurrence of cerebral nerve palsies in patients suffering from sarcoidosis has recently been emphasized by Longcope and Freeman.1 Facial paralysis, diplopia, strabismus, partial ptosis of the eyelids, either unilateral or bilateral, pupillary changes, involvement of the sensory portion of the trigeminal nerve, central deafness, dysarthria, paralysis of the vocal cords and of the soft palate, loss of taste, hypesthesia of one side of the tongue and dysphagia have all been encountered.Colover2recently reported three cases of sarcoidosis in which various cranial nerves were involved. In one there was bilateral facial palsy with ageusia. In another there were disturbed...Bibliography1. LongcopeFreeman WTDC: A study of sarcoidosis, Medicine 31: 1, 1952. CrossrefMedlineGoogle Scholar2. Colover J: Sarcoidosis with involvement of the nervous system, Brain 71: 451, 1948. CrossrefMedlineGoogle Scholar3. SonesIsraelDratmanFrank MHLMBJH: Effect of cortisone in sarcoidosis, New England J. Med. 244: 209, 1951. CrossrefMedlineGoogle Scholar4. GoldstonWeisenfeldBenjaminRosenbluth MSBMG: Effect of ACTH in chronic lung disease, Am. J. Med. 10: 166, 1951. CrossrefMedlineGoogle Scholar5. Siltzbach LB: Effects of cortisone in sarcoidosis, Am. J. Med. 12: 139, 1952. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Fort Howard, Maryland*Received for publication July 3, 1953.From the Department of Medicine, Veterans Administration Hospital, Fort Howard, Maryland. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byZur Klinik und Therapie des Morbus BoeckIntracranial Boeck's Sarcoid Tumor Resembling Meningioma 1 February 1954Volume 40, Issue 2Page: 356-361KeywordsCranial nervesDeafnessDysphagiaHospital medicineNervesParalysisPtosisSarcoidosisTasteTongue ePublished: 1 December 2008 Issue Published: 1 February 1954 PDF downloadLoading ...
Commentary: The reintroduction of Lotronex for diarrhea-predominant irritable bowel syndrome
Authors: Janet Woodcock
Journal: BMJ (2003)

From BMJ USA 2002;Nov:637 

The Food and Drug Administration approves program to provide patient access and manage risk

Immediately after the November 28, 2000 announcement of the safety-related withdrawal of Lotronex, distraught patients, stunned that this therapy had been taken away from them, began to contact the Food and Drug Administration (FDA). Thousands of individuals from all walks of life—businesspeople, military personnel, government employees, teachers, health care workers—wrote or emailed the agency, demanding access to a drug they characterized as “giving them their lives back.” Meanwhile, the drug's manufacturer, Glaxo Wellcome, was shutting down production lines and ongoing clinical trials, having rejected the FDA's proposal to create a limited access program for severely affected people. Subsequently, under ongoing pressure from patients, the manufacturer opened discussions with the FDA on potential drug availability programs. Thus began the arduous process of crafting a proposal for the reintroduction of Lotronex.

Lotronex had been withdrawn because outcomes from ischemic colitis (a known side effect) were more serious than predicted by the results of clinical trials and because of serious complications of constipation (a pharmacologic effect of a drug intended to reduce urgency and frequency). Cases of small bowel ischemia and a number of deaths had also been reported to the FDA. Irritable bowel syndrome (IBS) …
Differential memory function with dopaminergic versus anticholinergic treatment of drug-induced extrapyramidal symptoms
Authors: Maureen Fayen, Morris B. Goldman, Mark A. Moulthrop, Daniel J. Luchins
Journal: American Journal of Psychiatry (1988)

Nine chronic schizophrenic patients being treated with high-potency antipsychotic medication and antiparkinsonian agents were enrolled in a double-blind, crossover trial comparing amantadine and trihexyphenidyl. Memory function was assessed with the Rey Auditory-Verbal Learning Test during each 6-week drug trial. The subjects performed significantly better while receiving amantadine. Examinations of computed tomographic studies of seven subjects revealed a significant inverse correlation between ventricle size and memory while they were taking trihexyphenidyl but not amantadine. This suggests that patients with underlying brain pathology may be particularly vulnerable to the memory-disrupting effects of anticholinergic agents.
Sustained improvements in myocardial T2* over 2 years in severely iron‐overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine
Authors: Dudley J. Pennell, John B. Porter, Antonio Piga, Yong‐Rong Lai, Amal El‐Beshlawy, Mohsen Elalfy, Akif Yesilipek, Yurdanur Kilinç, Dany Habr, Khaled M. Musallam, Junwu Shen, Yesim Aydinok
Journal: American Journal of Hematology (2014)

Long-term controlled studies are needed to inform on the clinical benefit of chelation therapy for myocardial iron removal in transfusion-dependent beta thalassemia patients. In a 1-year nonrandomized extension to the CORDELIA study, data collected from patients with myocardial siderosis provided additional information on deferasirox or deferoxamine (DFO) efficacy and safety. Myocardial (m)T2* increased from baseline 11.6 to 15.9 ms in patients receiving deferasirox for 24 months (n = 74; geometric mean [Gmean ] ratio of month 24/baseline 1.38 [95% confidence interval 1.28, 1.49]) and from 10.8 to 14.2 ms in those receiving DFO (n = 29; Gmean ratio 1.33 [1.13, 1.55]; P = 0.93 between groups). Improved mT2* with deferasirox was evident across all subgroups evaluated irrespective of baseline myocardial (mT2* < 10 vs. ≥ 10 ms) or liver (LIC <15 vs. ≥15 mg Fe/g dw) iron burden. Mean LVEF was stable and remained within normal limits with deferasirox or DFO. Liver iron concentration decreased from high baseline values of 30.6 ± 18.0 to 14.4 ± 16.6 mg Fe/g dw at month 24 in deferasirox patients and from 36.8 ± 15.6 to 11.0 ± 12.1 mg Fe/g dw in DFO patients. The long-term safety profile of deferasirox or DFO was consistent with previous reports; serious drug-related AEs were reported in 6.8% of deferasirox and 6.9% of DFO patients. Continued treatment of severely iron-overloaded beta thalassemia patients with deferasirox or DFO led to sustained improvements in myocardial iron irrespective of high or low baseline myocardial or liver iron burden, in parallel with substantial improvements in liver iron (Clinicaltrials.gov identifier: NCT00600938).
Use of Preoperative Testing and Physicians’ Response to Professional Society Guidance
Authors: Alana E. Sigmund, Elizabeth R. Stevens, Jeanna D. Blitz, Joseph A. Ladapo
Journal: JAMA Internal Medicine (2015)

The value of routine preoperative testing before most surgical procedures is widely considered to be low. To improve the quality of preoperative care and reduce waste, 2 professional societies released guidance on use of routine preoperative testing in 2002, but researchers and policymakers remain concerned about the health and cost burden of low-value care in the preoperative setting.
Beyond the Ligand-Binding Pocket: Targeting Alternate Sites in Nuclear Receptors
Authors: Laura Caboni, David G. Lloyd
Journal: Medicinal Research Reviews (2012)

Nuclear receptors (NRs) are a family of ligand-modulated transcription factors with significant therapeutic relevance from metabolic disorders and inflammation to cancer, neurodegenerative, and psychiatric disorders. Drug discovery efforts are typically concentrated on modulating the natural ligand action within the ligand-binding pocket (LBP) in the C-terminal ligand-binding domain (LBD). Drawbacks of LBP-based strategies include physiological alterations due to disruption of ligand binding and difficulties in achieving tissue specificity. Furthermore, the lack of a "pure" and predictable mechanism of action predisposes such intervention toward drug resistance. Recent outstanding progress in our understanding of NR biology has shifted the focus of drug discovery efforts from inside to outside the LBP, affording consideration to the interaction between NRs and coactivator proteins, the interaction between NRs and DNA and the NRs' ligand-independent functions. This review encompasses such currently available NR non-LBP-based interventions and their potential application in therapy or as specific tools to probe NR biology.