tbuckley/cabot-search huggingface dataset:
Treatment of Metastatic Renal Cell Carcinoma With CAIX CAR-engineered T cells: Clinical Evaluation and Management of On-target Toxicity
Authors: Cor HJ Lamers, Stefan Sleijfer, Sabine van Steenbergen, Pascal van Elzakker, Brigitte van Krimpen, Corrien Groot, Arnold Vulto, Michael den Bakker, Egbert Oosterwijk, Reno Debets, Jan W Gratama
Journal: Molecular Therapy (2013)

Autologous T cells genetically modified to express a chimeric antibody receptor (CAR) against carboxy-anhydrase-IX (CAIX) were administered to 12 patients with CAIX-expressing metastatic renal cell carcinoma (RCC). Patients were treated in three cohorts with a maximum of 10 infusions of a total of 0.2 to 2.1 × 109 CAR T cells. CTC grade 2–4 liver enzyme disturbances occurred at the lowest CAR T cell doses, necessitating cessation of treatment in four out of eight patients in cohorts 1 and 2. Examination of liver biopsies revealed CAIX expression on bile duct epithelium with infiltration of T cells, including CAR T cells. Subsequently four patients were pre-treated with CAIX monoclonal antibody (mAb) G250 to prevent CAR-specific toxicity and showed no liver toxicities and indications for enhanced peripheral T cell persistence. No clinical responses were recorded. This report shows that CAIX-targeting CAR T cells exerted antigen-specific effects in vivo and induced liver toxicity at the lowest dose of 0.2 × 109 T cells applied, illustrating the potency of receptor-modified T cells. We provide in-patient proof that the observed "on-target" toxicity is antigen-directed and can be prevented by blocking antigenic sites in off-tumor organs and allowing higher T cell doses. Autologous T cells genetically modified to express a chimeric antibody receptor (CAR) against carboxy-anhydrase-IX (CAIX) were administered to 12 patients with CAIX-expressing metastatic renal cell carcinoma (RCC). Patients were treated in three cohorts with a maximum of 10 infusions of a total of 0.2 to 2.1 × 109 CAR T cells. CTC grade 2–4 liver enzyme disturbances occurred at the lowest CAR T cell doses, necessitating cessation of treatment in four out of eight patients in cohorts 1 and 2. Examination of liver biopsies revealed CAIX expression on bile duct epithelium with infiltration of T cells, including CAR T cells. Subsequently four patients were pre-treated with CAIX monoclonal antibody (mAb) G250 to prevent CAR-specific toxicity and showed no liver toxicities and indications for enhanced peripheral T cell persistence. No clinical responses were recorded. This report shows that CAIX-targeting CAR T cells exerted antigen-specific effects in vivo and induced liver toxicity at the lowest dose of 0.2 × 109 T cells applied, illustrating the potency of receptor-modified T cells. We provide in-patient proof that the observed "on-target" toxicity is antigen-directed and can be prevented by blocking antigenic sites in off-tumor organs and allowing higher T cell doses.
Vale of Leven Hospital
Authors: J. Campbell
Journal: BMJ (1960)

<h3>BACKGROUND/AIMS</h3> To investigate the in vitro effect of a short time exposure to the anthracycline idarubicin on proliferation, protein synthesis, and motility of human Tenon’s capsule fibroblasts in comparison with the antitumour antibiotic mitomycin C. <h3>METHODS</h3> After determination of effective concentrations of idarubicin, fibroblasts of the human Tenon’s capsule were exposed to idarubicin or mitomycin C at concentrations ranging from 0.1 μg/ml to 1 μg/ml or from 2.5 μg/ml to 250 μg/ml, respectively, for 0.5, 2, or 5 minutes and cultured for 60 days. Cell death by apoptosis caused by idarubicin treatment was confirmed by Hoechst 33258 staining. Further proliferation was explored by cell counting and by<sup>3</sup>H-thymidine uptake. Protein synthesis was measured by<sup>3</sup>H-proline uptake and motility was assessed by agarose droplet motility assay. <h3>RESULTS</h3> Idarubicin is able to exert toxicity and to induce apoptosis during a short time exposure of 0.5 minutes at concentrations of 0.3–1 μg/ml resulting in a significant reduction in cell number compared with the control after 60 days. For mitomycin C, higher concentrations and longer expositions were necessary. Even after treatment with 1 μg/ml idarubicin or 250 μg/ml mitomycin C a few cells were able to incorporate <sup>3</sup>H-thymidine. <sup>3</sup>H-proline uptake up to 10 days after exposure to 0.3 μg/ml idarubicin was found not to be decreased. Cell motility was reduced after treatment with 1 μg/ml idarubicin for 5 minutes or with 250 μg/ml mitomycin C for 2 or 5 minutes. For low mitomycin C concentrations, an increase in motility was found during the first 10 days. <h3>CONCLUSION</h3> Idarubicin reduces proliferation of human Tenons’s capsule fibroblasts after incubation for 0.5 minutes at concentrations as low as 0.3–1 μg/ml. In comparison, mitomycin C requires longer exposure times and higher doses for equal results. Therefore, idarubicin may be useful in the prevention of glaucoma filtering surgery failure.
Hairy‐cell leukemia associated with Hodgkin's disease: A case report
Authors: Everett E. Vokes, Mitchell A. Bitter, Michael B. Prystowsky, William O'Reilly, Harvey M. Golomb
Journal: American Journal of Hematology (1985)

Abstract A 56‐year‐old man who had easy bruising, an enlarged left supraclavicular lymph node, and splenomegaly was diagnosed as having hairy‐cell leukemia. Treatment consisted of splenectomy. Because of progressive lymphadenopathy in the following months, the patient required reevaluation. Examination of a lymph node biopsy specimen now revealed Hodgkin's disease, nodular sclerosis. This is the first pathologically confirmed case of hairy‐cell leukemia coexisting with Hodgkin's disease.
AN ALL-BRITISH MYCOLOGICAL CULTURE MEDIUM
Authors: GWENDOLINE I. M. CARLIER
Journal: British Journal of Dermatology (1948)

Journal Article AN ALL‐BRITISH MYCOLOGICAL CULTURE MEDIUM Get access GWENDOLINE I. M. CARLIER, M.Sc. GWENDOLINE I. M. CARLIER, M.Sc. The Skin Hospital, Birmingham Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 60, Issue 2, 1 February 1948, Pages 61–63, https://doi.org/10.1111/j.1365-2133.1948.tb10992.x Published: 01 February 1948
Compulsory screening of immigrants for tuberculosis and HIV
Authors: Richard Coker
Journal: BMJ (2004)

Is not based on adequate evidence, and has practical and ethical problems 

Increased movements of peoples are stressing public health responses to threats from communicable diseases internationally. This year several bodies in the United Kingdom, including the Conservative party, have called for compulsory screening of immigrant populations for tuberculosis and HIV in order to support national efforts to control these communicable diseases. Given that concerns about asylum policy are consistently high on the political agenda, and that the media have recently taken to conflating anti-immigrant sentiments with public health threats through communicable diseases,1 the government may be considering compulsory screening of immigrants for some infectious diseases. But is there a rational public health argument that is grounded in evidence for compulsory screening of immigrants?

For tuberculosis and HIV the purpose of screening should be twofold—to identify cases early such that individuals can be offered treatment and care, and so to inhibit further transmission (through treatment, behaviour change, or isolation) to protect public health.

For tuberculosis the notion that screening immigrants detects those with the disease and therefore benefits public health is not straightforward. Although the increase in rates of tuberculosis in England and Wales over the past decade is clearly associated with immigrants, this does not translate into a cogent argument in favour of screening immigrants, never mind compulsory screening.2

Most active tubercular disease seems to develop after immigration.3 Clearly, those individuals in whom tuberculosis is identified early can benefit from treatment, but little evidence exists to show that early detection of tuberculosis in foreign born individuals conveys appreciable public health …
Cardiac Failure in Transgenic Mice With Myocardial Expression of Tumor Necrosis Factor-α
Authors: Debora Bryant, Lisa Becker, James Richardson, John Shelton, Fatima Franco, Ronald Peshock, Marita Thompson, Brett Giroir
Journal: Circulation (1998)

Background —Tumor necrosis factor-α (TNF-α) is a multifunctional cytokine that has been detected in several human cardiac-related conditions, including congestive heart failure and septic cardiomyopathy. In these conditions, the origin of TNF-α secretion is, at least in part, cardiac myocytes. Methods and Results —To determine the consequences of TNF-α production by cardiac myocytes in vivo, we developed transgenic mice in which expression of a murine TNF-α coding sequence was driven by the murine α-myosin heavy chain promoter. Four transgenic founders developed an identical illness consisting of tachypnea, decreased activity, and hunched posture. In vivo, ECG-gated MRI of symptomatic transgenic mice documented a severe impairment of cardiac function evidenced by biventricular dilatation and depressed ejection fractions. All transgenic mice died prematurely. Pathological examination of affected animals revealed a globular dilated heart, bilateral pleural effusions, myocyte apoptosis, and transmural myocarditis in both the right and left ventricular free walls, septum, and atrial chambers. In all terminally ill animals, there was significant biventricular fibrosis and atrial thrombosis. Conclusions —This is the first report detailing the effects of tissue-specific production of TNF-α by cardiac myocytes in vivo. These findings indicate that production of TNF-α by cardiac myocytes is sufficient to cause severe cardiac disease and support a causal role for this cytokine in the pathogenesis of human cardiac disease.
Abstract 2641: Diversity of anticancer mechanisms of action of tritepenoids derived from betulinic acid
Authors: Petr Dzubak, Jiri Rehulka, Dusan Holub, Tomas Ozdian, Anna Janostakova, Jan Sarek, Martin Vlk, Marian Hajduch
Journal: Cancer Research (2011)

Abstract Betulinic acid and its derivatives are cytotoxic compounds with the specific effect to the tumor cells. In our betulinic acid derivative chemical library we have identified several potent compounds which were highly active in the wide spectrum of the cancer cell lines and the primary tumour cells as well as. Cell cycle modulating effects of selected compounds were monitored and surprisingly the compounds with different effect on the cell cycle profile were observed. Some derivatives were inhibiting the progression through the early S or G2-M phases and some were rapidly inducing the apoptosis. To identify the mechanisms of the action we have used genomic expressional (Affymetrix) and proteomic profiling (LC-MS/MS, SILAC). Derivatives inducing the rapid induction of the apoptosis were identified to regulate and affect the mRNA expression of the genes and proteins closely related to the oxidative stress and to the detoxification enzymes. Glutathione detoxification pathway and the oxidative phosphorylation cascade (upregulation of glutathion peroxidase, peroxiredoxine, thioredoxin, sulfiredoxine, cytochrome c oxidase, down regulation of glutathion S transferase) were affected and direct interaction of derivatives with cytochrome c was observed. All previously mentioned mechanisms are closely related to the mitochondrion damage. However, derivatives inducing the G2/M block were also increasing the expression of the tubulin chaperone cofactor A (TBCA) and the underexpression of other proteins like chaperonin containing TCP1, subunit 3 (CCT3) related to tubulin polymerization pathway and cell cycle regulation. Tubulin chaperone cofactors were recently suggested to be potential targets for the cancer therapy and current works are showing the upregulation of tubulin chaperone cofactor C correlated to the suppression of the tumor growth and increased chemosensitivity in resistant cancer phenotypes. This work was supported by the GACR 301/09/P433, GACR 305/09/1216 and CZ.1.05/2.1.00/01.0030). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2641. doi:10.1158/1538-7445.AM2011-2641
Syphilis and Drunkenness.
Authors: Evan O'Neill Kane
Journal: JAMA (1897)

Kane, Pa., May 8, 1897. <h3>To the Editor:</h3> —In closing a recent editorial entitled "Legislation against Degeneracy," (April 17) our editor touches the key-note of the situation. Having clearly proven in the preceding paragraphs the futility as well as the injustice of all legal restriction imposed upon the marriage of epileptic and insane, he ends by saying: " The only real safeguards against the propogation of degenerates are to be looked for in the higher moral education of the public and the cultivation of practical moral standards." How are we to attain these practical moral standards? As our editor remarks, immorality and illegitimate births will be greatly increased if we are to render it illegal for those of epileptic, insane or tubercular tendencies to marry. While, too, it can not be denied that their taints do often exist as an inheritance, it is equally true that, given a suitable environment and
In vitro effects of Epstein-Barr virus on peripheral blood mononuclear cells from patients with rheumatoid arthritis and normal subjects.
Authors: L Slaughter, D A Carson, F C Jensen, T L Holbrook, J H Vaughan
Journal: The Journal of Experimental Medicine (1978)

Peripheral blood mononuclear cells from 10 patients with rheumatoid arthritis and 9 control subjects were cultured in vitro for 30 days with and without infection by Epstein-Barr virus. All cultures showed polyclonal stimulation of B cells as indicated by rising levels of IgM in the culture supernates, reaching maximal at 18-24 days, and with no quantitative or kinetic difference between the RA and control cells. IgM anti-IgG was also produced in both groups and maximally at 18-24 days, but in greater quantity by the RA lymphocytes. The anti-IgG made by the RA lymphocytes was more easily absorbed by solid phase IgG than was the anti-IgG made by the normal lymphocytes and thus was judged to be of higher affinity. RA lymphocytes uninfected with EBV had higher transformation scores than did the normal controls and developed spontaneously into permanent cell lines in six instances.
THE TESTIS HORMONE
Authors: CARL R. MOORE
Journal: JAMA (1935)

<h3>Note.—</h3> This article and the articles in the previous issues ofThe Journalare part of a series published under the auspices of the Council on Pharmacy and Chemistry. Other articles will appear in succeeding issues. When completed, the series will be published in book form.—Ed. The testicle exercises at least two biologic functions of utility in the organism, the primary of which is maturation of germ cells and the secondary the secretion of one or more substances known as the testis hormone. The primary function is much the older and is exercised not only in vertebrates but in invertebrates as well. Hormone secretion, however, appears to be restricted to the vertebrates and to have undergone a gradual increase in complexity; it is on the accessory organs of reproduction that the influence of the testicular hormone is exercised. In some lower fish the sex cells are merely liberated from the gonad
Pharmacological, Convulsive and Other Somatic Treatments in Psychiatry
Authors: Samuel Friedman
Journal: JAMA (1970)

It is good to welcome again a familiar friend, dressed in his old, comfortable clothes but refurbished with a few new bits of finery. Regretfully, one must also record the death of Paul Hock, the previous coauthor. Dr. Hanns Hippius of Germany has replaced him as Kalinowsky's associate. In less than a quarter of a century, this book has gone through four editions. The present one weighs twice as much as the original. In the current volume, "pharmacological" has replaced "shock treatments" as the key word in the title. Despite this, electric shock therapy (EST), insulin, and psychosurgery occupy the major portion of the book, namely 175 pages; and pharmacotherapy, 150 pages. Regardless of one's personal viewpoint concerning treatment methods, the sections on nonpharmacological somatic therapies have at least great historical importance. Kalinowsky continues to advocate insulin coma treatments and states, "... this method should be retained as an important tool
Ultraperil of Diagnostic Ultrasound
Authors: Judith Everett
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The current vogue of preempting diagnoses of possible malignancies in renal masses by ultrasound has led me to express a word of caution. The pattern of ("benign") renal<i>cyst</i>by ultrasound may lead to nonsurgery or use of needle aspiration techniques on the basis of a standing protocol for management. <h3>Report of a Case.—</h3> A 72-year-old woman had the intriguing history of a stroke five years earlier as a result of "too many red blood corpuscles." She was mildly hypertensive and had a hemoglobin value of 19.0 gm/100 ml by venipuncture. She had florid facies and gross clubbing of the fingers. No studies other than cerebral angiography had been done at the small hospital at which she had been previously. An intravenous pyelogram disclosed a right renal mass and, on the basis of ultrasound findings consistent with "cyst," a debate arose as to whether surgery should or
Effectiveness of Lithium Carbonate in the Treatment of Manic-Depressive Illness
Authors: CHRISTIAAN D. VAN DER VELDE
Journal: American Journal of Psychiatry (1970)

The author reports on the responses to lithium cabonate of 75 manic-depressive patients. Lithium carbonate was found to be highly effective in the acute manic state but without merit in the treatment of acute depression. Its efficacy was inversely related to age. Response to the drug varied in some patients; a positive response at one time was no guarantee for a similar response in subsequent trials. The possibility of different biochemical states underlying similar clinical states is discussed.
Thyroid Autoimmunity at Onset of Type 1 Diabetes as a Predictor of Thyroid Dysfunction
Authors: Gemma C. González, Ismael Capel, José Rodríguez-Espinosa, Didac Mauricio, Alberto de Leiva, Antonio Pérez
Journal: Diabetes Care (2007)

Type 1 diabetes and autoimmune thyroid diseases (AITDs) often coexist in the same individual and in the same family. In the general population, AITD is more frequent in female subjects and prevalence increases with age. In diabetic patients, age and sex distributions are similar, but the prevalence is higher and increases with duration of the disease (1–3,4). Thyroid dysfunction can affect metabolic control in type 1 diabetes, and some studies (3) have shown a higher severity of diabetes when it is associated with AITD, although other studies (4) did not find these differences. Nevertheless, there is general agreement (5,6) on the utility of systematic screening of AITD in the type 1 diabetes population given its high prevalence, but procedure and frequency remain controversial. The aim of the present study was to determine the presence of thyroid autoantibodies at type 1 diabetes onset and its predictive capacity for the future development of thyroid dysfunction.

Between September 1987 and January 1994, 204 patients were consecutively diagnosed with type 1 diabetes at our institution. One patient had developed primary hypothyroidism 3 years before the development of type 1 diabetes, 10 patients were not followed up after a few months from diagnosis, and thyroid autoimmunity at diagnosis was not determined in 17 patients. The remaining 176 patients were included in the study. The mean age at diabetes diagnosis was 24.4 ± 9.4 years, 65% were male …
CN-02 * MYELOPATHY FOLLOWING INTRATHECAL CHEMOTHERAPY: A CASE SERIES IN ADULTS
Authors: D. Cachia, C. Kamiya-Matsouka, L. Chi, C. Pinnix, N. Daver, K. Woodman
Journal: Neuro-Oncology (2014)

Intrathecal (IT) chemotherapy in combination with systemic chemotherapy is an effective treatment modality used in the prophylaxis and treatment of CNS disease in hematological malignancies. IT agents commonly used in various chemotherapeutic regimens include methotrexate and cytarabine arabinoside (Ara-C).Side effects from IT chemotherapies described in the literature vary from mild asymptomatic forms of arachnoiditis diagnosed on MRI to leukoencephalopathy and myelopathy. These complications have been reported more frequently in the pediatric literature than in adults. We here describe 7 adult patients treated at a single institution for hematological malignancies that developed myelopathy following intrathecal chemotherapy. 5 out of our 7 patients demonstrated longitudinal hyperintenities involving mostly the dorsal columns and to varying degrees the lateral corticospinal tracts; a picture suggesting methotrexate induced toxicity. In the 2 cases where myelobasic protein was checked in the CSF, it was significantly elevated supporting the role of a potential CSF biomarker to diagnose cord injury and distinguish the pathology from leukemic infiltration. Median survival was 3.1 months from the time of myelopathy diagnosis despite various treatment strategies employed. We did not find any correlation between number of IT methotrexate doses given and development of myelopathy indicating a potential individual sensitivity to methotrexate. Based on what is known, immediate discontinuation of intrathecal methotrexate treatment would be recommended once a diagnosis of IT induced melopathy is made with consideration of methionine or S-adenosylmethionine supplementation for patients who received IT methotrexate.
Antagonistic Effect of Oral Vitamin K1 on the Action of Ethyl Biscoumacetate and Phenylindanedione
Authors: J. N. M. Chalmers, M. F. Dixon, W. Polack
Journal: BMJ (1954)

<b>1979</b> <h3><b>Objectives</b></h3> Skeletal tuberculosis can mimic malignant lesion with its destruction of bones and increased FDG uptake on PET imaging. This study aimed to investigate the feature of such kind lesion in PET/CT imaging, hoping to improve the diagnostic accuracy. <h3><b>Methods</b></h3> From Jan 2009 till Sep 2012, 87 patients with FDG-avid bone lesion(s) caused by unknown reason were included in the study. All patients undertook the FDG PET/CT scan 60min after the injection of about 10mCi 18F-FDG. <h3><b>Results</b></h3> Among all 87 patients, 19 patients were confirmed of skeletal tuberculosis by pathology or by following anti-tuberculosis treatment. The mean SUVmax was 8.3 (4.4~15.9); 12 patients had clinical symptoms (low fever, night sweat, etc.); 15 were multi-lesions (78.9%), including multiple involvement in lymph nodes or organs; 4 were single lesion (21.1%). All patients had vertebrae involvement, 12 located in lumbar vertebrae. 6 patients (31.6%) had a confirmed history of pulmonary tuberculosis; Calcifications in lungs or hilar lymph nodes were seen in 8 patients on CT images (42.1%). <h3><b>Conclusions</b></h3> For patients with FDG-avid bone lesions by unknown causes, skeletal tuberculosis should be considered. Though the diagnostic specificity of PET/CT in skeletal tuberculosis is not satisfying, it can be used to locate the site of biopsy. The clinical symptoms (low fever, night sweat, etc.), previous history of tuberculosis and calcification findings on CT images may help to improve the accuracy of diagnosis.