tbuckley/cabot-search huggingface dataset:
Drugs acting on the intracellular signalling system
Authors: Yasuyuki Nomura, Yoshihisa Kitamura, Michihisa Tohda, Yukiko Tokumitsu
Journal: Medicinal Research Reviews (1993)

Cellular response to extracellular messages is a basic process to maintain and to support cell life. Several signalling molecules important as sites of therapeutic drug action are involved in the response. Recent studies on life sciences have elucidated molecular properties of intracellular signalling factors and mechanisms of cascading. Novel drugs acting on signalling molecules and possessing new sites and mechanisms of action have been found. This article summarizes the properties (subtypes, structures, functions) of signalling factors (receptors, ion channels, GTP binding proteins, second messenger-generating enzymes, second messenger-metabolizing enzymes, second messengers protein kinases, protein phosphatases) and lists in Tables A-H drugs that act on signalling molecules and which should find clinical use.
Letter: Congenital absence of vagina.
Authors: J M Beazley
Journal: BMJ (1974)

impressions, however skilled and experienced the observer, cannot answer the sort of questions posed by Dr. Davies.Spirometry provides the only proven tests that have been used on a large scale for measuring changes in respiratory function over a pro- longed period.In common with other research groups we are now using tests which have been suggested as possibly more appro- priate for the study of diseases of the small airways, but the results will not be avail- able for some time.Dr. Davies restates the interesting hypothesis that chronic bronchitis may protect men from developing pneumoconiosis.He cites recent work showing that relatively large particles (> 3 ,um) have a reduced probability of reaching the alveoli.Effects on smaller particles which form the bulk of the dust in miners' lungs (mostly 1 ,um diameter) are unknown.These specula- tive ideas are being kept under review and may help to explain future findings, but they cannot be used as serious evidence at present.Neither the medical service of the National Coal Board nor the Institute of Occupational Medicine is responsible for the administra- tion and operation of the compensation machinery.These are managed by the De- partment of Health and Social Security.Our function is to engage in research on diseases of coalminers and to publish the facts.This we have done and will continue to do.-We are, etc.,
The Undereducated Physician's Therapeutic Decisions
Authors: Kenneth L. Melmon, Terrence F. Blaschke
Journal: New England Journal of Medicine (1983)

In this issue of the Journal Avorn and Soumerai claim that highly motivated and highly trained doctors of pharmacy can enhance the quality of therapeutic decisions by practicing physicians.1 The authors develop several premises. One is that generally available information that would lead physicians to better prescribing behavior is often not used in making therapeutic decisions. Unquestionably, at least one of the drugs whose use they studied illustrates their point. Propoxyphene is a drug with limited analgesic efficacy and a much higher incidence of toxicity than is associated with commonly used, quite efficacious, and much cheaper agents. On the other . . .
Analysis of action potentials in the canine ventricular septum: No phenotypic expression of M cells
Authors: S MORITA, D ZIPES, H MORITA, J WU
Journal: Cardiovascular Research (2007)

Objective: Transmural heterogeneity in the ventricular free wall, enhanced by the midmyocardial long action potential duration (APD) of M cells, plays an important role in the arrhythmogenesis of long QT syndrome. Although we observed dynamic expression of M cell phenotypes in the canine ventricular free wall, it is still unclear whether similar phenomena are present in the interventricular septum. This study evaluated transmural heterogeneity of APD in the septum. Methods: We isolated and perfused 22 canine septal preparations through the septal branch of the anterior descending coronary artery, and optically mapped 256 channels of action potentials on their cut-exposed transseptal surfaces before and after treatment with sotalol (IKr blocker), anemone toxin II (ATX-II, which slows the inactivation of INa), or drug-free state in 6, 9, and 22 preparations, respectively. The preparations were paced from the left ventricular endocardium at cycle lengths of 500, 1000, 2000, and 4000 ms. Results: We observed progressively lengthening of APD across the septum from the right ventricular to the left ventricular endocardium without a midmyocardial maximum under all conditions. All action potentials had minor phase-1 notches, resembling the endocardial action potential in the ventricular free wall. Increasing cycle lengths and concentrations of sotalol and ATX-II prolonged APD without midmyocardial preference and increased the transseptal dispersion of APDs. Conclusions: Canine interventricular septal action potentials are similar in shape to the endocardial action potentials in the ventricular free wall, with smooth transseptal transition in APD. We found no phenotypical expression of M cells in the canine interventricular septum.
Milk-borne campylobacter infection.
Authors: D A Robinson, D M Jones
Journal: BMJ (1981)

The common factor in 13 recent outbreaks of Campylobacter jejuni enteritis was the consumption of unpasteurised or incompletely pasteurised milk. C jejuni is a common commensal in the alimentary tract of milking cows, but it is not clear how the milk becomes contaminated with the organism. Pasteurisation will readily eliminate the organism from milk. In England and Wales 3% of milk retailed is still unpasteurised, and in the light of these findings it is suggested that only pasteurised milk should be sold to the public.
Abstract 5663: In vitro radiosensitization of human cervical cancer HeLa cells with iron oxide- titanium dioxide core-shell nanoparticles conjugated with 3,4-Dihydroxyphenylacetic acid (DOPAC).
Authors: Salida Mirzoeva, Beau M. Wanzer, Tatjana Paunesku, Gayle E. Woloschak
Journal: Cancer Research (2013)

Abstract Cervical cancer is resistant to current surgical, chemo- and radiotherapy interventions and represents a virtually incurable tumor. In this study, we explored titanium dioxide core-shell nanocomposites conjugated with DOPAC (DOPAC-NCs) as radiosensitizers. Radioresistant human carcinoma cervical HeLa cell cultures were treated with or without of increasing concentrations of DOPAC-NCs (5-20 nM) prior to irradiation. One hour later, cells were irradiated with a single dose of gamma radiation (5 Gy, 10 Gy, or 15 Gy). Seventy-two hours following radiation treatment, cell proliferation/viability was assessed by MTS assay. Sham-irradiated cells were served as a control. We have found that treatment of HeLa cells with DOPAC-NCs affected the survival of irradiated cells in a dose-dependent manner. Our data demonstrate that cell survival of cells irradiated with 15 Gy and pre-treated with the highest concentration of DOPAC-NCs was as low as 23.7% compared to survival of cells that were not treated with DOPAC-NCs prior to irradiation. In opposite, without radiation, treatment with DOPAC-NCs had no effect on cell viability/proliferation. These findings provide in vitro evidence that DOPAC-NCs may be developed and employed as radiosensitizers in cervical cancer radiation therapy. Citation Format: Salida Mirzoeva, Beau M. Wanzer, Tatjana Paunesku, Gayle E. Woloschak. In vitro radiosensitization of human cervical cancer HeLa cells with iron oxide- titanium dioxide core-shell nanoparticles conjugated with 3,4-Dihydroxyphenylacetic acid (DOPAC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5663. doi:10.1158/1538-7445.AM2013-5663
Persistence of an Abnormal Pattern on 99mTc Pyrophosphate Myocardial Scintigraphy Following Acute Myocardial Infarction
Authors: Kenneth P. Lyons, Harold G. Olson, W. Theron Brown, Wilbert S. Aronow, John Kuperus
Journal: Clinical Nuclear Medicine (1976)

Seventy patients, 69 males and one female, were studied by 99mTc pyrophosphate myocardial scintig-raphy more than six weeks after a documented myocardial infarction. History, physical examination, ECG, and serum enzyme measurements were obtained at the time of scintigraphy. All 70 patients were outpatients with no evidence of recurrent infarction since their myocardial infarction. Sixty-four of the 70 patients had angina pectoris or congestive heart failure. The scintigrams were interpreted by two observers. Images were scored on a scale of 1 + to 3 + for intensity of myocardial activity and were either diffuse or regional in distribution. Activity of 2 + or greater was considered positive. Of the 70 patients, 36 (51%) had myocardial scintigrams which were interpreted as positive for acute myocardial infarction and 34 (49%) as negative for acute myocardial infarction. Correlation of the clinical status with the scintigram revealed the following: all six asymptomatic patients had negative scintigrams; of the 32 patients with Class II angina, 15 were positive and 17 were negative; 10 of 14 patients with Class III angina were positive; 8 of 11 with angina and congestive heart failure (CHF) were positive; and 3 of 7 with CHF alone had positive scintigrams. In 54 of the patients who had previous scintigraphy at the time of acute infarction, the followup scintigram showed definite improvement in 48 patients and was the same or worse in 6 patients. Of these 6 patients, 2 showed scintigraphic evidence of reinfarction with a focal abnormality involving a different wall than on the original study. Furthermore, these were the only 2 among the 70 patients where the myocardial activity was graded at 3 +. Therefore, patients who have had previous myocardial infarctions with no clinical evidence of recurrent infarction may have persistent abnormalities on repeat myocardial scintigraphy. Meaningful interpretation is possible, however, by correlation with the clinical status and comparison with previous scintigraphy.
Src homology 2 domain–containing inositol 5-phosphatase 1 deficiency leads to a spontaneous allergic inflammation in the murine lung
Authors: Sun-Young Oh, Tao Zheng, Monica L. Bailey, Dwayne L. Barber, John T. Schroeder, Yoon-Keun Kim, Zhou Zhu
Journal: Journal of Allergy and Clinical Immunology (2006)
Abstract 1981: Ephrin B2 as a tumor suppressor in breast cancer.
Authors: Gizeh Perez-Tenorio, Olle Stål, Elena B. Pasquale
Journal: Cancer Research (2013)

Abstract The EphB4 is a tyrosine kinase receptor with both tumor suppressor and promoting activities. The role of EphB4 in breast cancer is not fully elucidated. EphB-receptors transmit forward and reverse signals, which together are known as bidirectional signals. EphB4 reverse signaling, mediated by the ephrin-B2 ligand expressed in endothelial cells, causes some of the oncogenic properties of the receptor. In contrast, EphB4 forward signaling suppresses tumor growth. In breast cancers with high EphB4-receptor expression the forward signaling activity is low due to low expression of ephrin-B2. In fact, the EFNB2 gene, encoding ephrin-B2, is located on chromosome 13, which is lost in more than 30% of breast cancers. Our hypothesis was that ephrin-B2 re-expression in tumors could restore EphB4-forward signal inhibiting tumor growth. To examine the effects of EphB4-ephrin-B2 co-expression in vitro, we used lentiviral vectors to stably infect MCF7 cells with ephrin-B2. We found in vitro that ephrin-B2 expression caused cell detachment, inhibited cell proliferation; focus formation and cell motility, all characteristics of tumor suppression. Likewise, in patient materials we observed that high ephrin-B2 mRNA levels correlated with better distant recurrence-free survival. Interestingly, low ephrin-B2 expression identifies the group of worse prognosis among patients with high EphB4 and HER-2 expression in terms of distant recurrence and breast cancer survival. Taken together these results support our hypothesis and suggest that ephrin-B2 may be a tumor suppressor and a novel prognostic marker in breast cancer. Citation Format: Gizeh Perez-Tenorio, Olle Stål, Elena B. Pasquale. Ephrin B2 as a tumor suppressor in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1981. doi:10.1158/1538-7445.AM2013-1981
Two health centres are finalists in top UK architecture prize
Authors: J. Wise
Journal: BMJ (2009)

<h3>Background</h3> The first-in-class oral inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) palbociclib, combined with hormonal therapy, is a new standard of treatment in the first and second line for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). <h3>Purpose</h3> To describe the effectiveness and safety of palbociclib combination therapy for mBC in clinical practice. <h3>Material and methods</h3> Retrospective and observational study in which the effectiveness and safety of palbociclib was tested by reviewing medical and pharmaceutical records of all patients treated with the drug from December 2015 until April 2018 in a tertiary hospital. Dispensation data was obtained from the Pharmacy Department’s software, Farmatools. Collected data included: age, ECOG performance status, number of cycles received, duration and prior lines of treatment. Effectiveness endpoint was progression-free survival (PFS) according to RECIST version 1.1. Adverse events (AEs) related to treatment with palbociclib and registered in the patient’s medical records were included in the study. Toxicity was evaluated as defined by the NCI-CTCAE, version 4.0. <h3>Results</h3> <h3>Conclusion</h3> A significant difference in PFS was observed compared to published clinical trials PALOMA-2 (PFS 24.8 months) and PALOMA-3 (PFS 11.2 months). Otherwise, palbociclib showed a similar safety profile. However, further studies are required to establish effectiveness in clinical practice as 19/29 patients are still receiving treatment. <h3>References and/or acknowledgements</h3> 1. Palbociclib: EPAR-Summary for the public. EMA. 2. Pivotal studies PALOMA-2 and PALOMA-3. No conflict of interest.
Screening for thyroid disease in a primary care unit with a thyroid stimulating hormone assay with a low detection limit.
Authors: R. Eggertsen, K. Petersen, P. A. Lundberg, E. Nystrom, G. Lindstedt
Journal: BMJ (1988)

In a study at a primary care centre in a predominantly rural area of Sweden the records of all patients with established thyroid disease were scrutinised and 2000 consecutive adult patients screened with an immunoenzymometric thyroid stimulating hormone assay. The aims of the study were fourfold: firstly, to assess the total burden of thyroid disease in primary care centres in Sweden; secondly, to assess the efficacy of clinical diagnosis of the disease in unselected populations of patients; thirdly, to assess the efficacy of clinical evaluation of treatment with thyroxine; and, lastly, to see whether a single analysis of the serum thyroid stimulating hormone concentration by recent methods would be enough to identify an abnormality of thyroid function. Of the roughly 17,400 adults in the study community, 111 women and 10 men were being treated for thyroid disease. Screening detected 68 patients (3.5%) not receiving thyroxine who had a serum thyroid stimulating hormone concentration of 0.20 mU/l or less, all of whom were followed up clinically. Fifty of these patients were also studied biochemically during follow up. Only nine of the 68 patients had thyroid disease (three with thyrotoxicosis requiring treatment), no evidence of the disease being found in the remainder. Sixteen patients had spontaneous hypothyroidism requiring treatment, and neither these nor three patients with thyrotoxicosis had been detected at the preceding clinical examination. Of 35 patients in whom thyroid disease was suspected clinically at screening, none had laboratory evidence of thyroid dysfunction. In this series 1.3% of all women in the study community (2.6% of all 50-59 year olds) and 0.1% of the men were being treated for thyroid disease at the primary care centre, roughly 1.0% of adults subjected to screening were found to have thyroid disease requiring treatment, and most patients with a thyroid stimulating hormone concentration of 0.20 mU/l or less did not have thyroid dysfunction. It is concluded that measuring the basal serum thyroid stimulating hormone concentration by present methods is insufficient for the biochemical assessment of thyroid dysfunction in unselected populations.
Ankylosing (Rheumatoid) Spondylitis
Authors: John W. Sigler
Journal: JAMA (1965)

The purpose of the exhibit was to emphasize the salient features, subtle signs, and management of anklyosing spondylitis. Usually spondylitis is easily recognized in advanced stages, but if deformity is to be minimized, early detection is essential. Prompt institution of a comprehensive program of management will do much to preserve functional posture. <h3>Diagnosis</h3> Spondylitis should be suspected in the presence of the following symptoms: recurrent low back pain (frequently nocturnal), alternating right- and left-sided sciatic pain, morning stiffness and soreness in the back, restriction of chest expansion, or girdle or peripheral joint synovitis. Hip, shoulder, and peripheral joint synovitis commonly occur and frequently are overlooked as manifestations of ankylosing spondylitis. Ankylosing spondylitis occurs in both sexes, males preponderating 7:1. In mild disease there is usually no systemic disturbance. In more severe illness, fever, fatigue, anorexia, and weight loss are often present. The most frequent complication of ankylosing spondylitis is iritis,
Stimulation of Hematopoiesis by Androgenic Hormone.
Authors: B. J. Kennedy
Journal: Annals of Internal Medicine (1964)

s1 February 1964Stimulation of Hematopoiesis by Androgenic Hormone.B. J. Kennedy, M.D., F.A.C.P.B. J. Kennedy, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-2-327_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAndrogenic hormone increases erythropoiesis when administered in massive doses for a prolonged period. Furthermore, in depression of bone marrow function by toxic agents or disease, improvement of leukopenia and thrombocytopenia have been inconsistently observed.Androgenic hormones have been administered to patients with advanced malignancies in an attempt to allow chemotherapeutic agents to be employed more effectively. The hormone was administered to patients with (1) depressed marrow due to tumor; (2) depressed marrow due to previous cytotoxic therapy or irradiation therapy; and (3) normal marrow prior to intensive cytotoxic therapy. When the androgenic hormone was administered for more than 6 weeks,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Minneapolis, Minnesota PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1964Volume 60, Issue 2_Part_1Page: 327-327KeywordsBone marrowChemotherapeutic agentsErythropoiesisHematopoiesisHormonesToxic agents Issue Published: 1 February 1964 PDF DownloadLoading ...
The Care of the Baby’s Eyes in the Perambulator
Authors: Mary E. Baldwin
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 2138: Targeting cancer-associated fibroblasts using antibodies recognizing fibroblast activation protein-alpha.
Authors: James A. Van Deventer, Karl D. Wittrup
Journal: Cancer Research (2013)

Abstract An expanding body of work suggests that the tumor stroma plays an integral role in the initiation and development of epithelial cancers. Within the stroma, cancer-associated fibroblasts (CAFs) are involved in several functions that form integral aspects of tumor progression, including immune suppression, metabolism, and invasion and metastasis. Despite the demonstrated importance of CAFs within the tumor microenvironment, targeting CAFs in a therapeutic context remains a challenge. The work presented here details the isolation and characterization of antibody fragments targeting multiple epitopes of fibroblast activation protein-alpha (FAP), a membrane-bound protease selectively overexpressed on CAFs in numerous epithelial cancers. The combination of a minimalist antibody fragment library and yeast surface display allowed for the isolation of more than 50 unique antibodies recognizing the human or murine forms of FAP, with close to 30 exhibiting cross-reactivity. To narrow the pool of cross-reactive antibodies to a biologically relevant subset, the fragments were converted to an antibody-like format that could be secreted from yeast. Without purification, the soluble proteins were first used to investigate the abilities of individual fragments to recognize FAP transiently expressed on the surface of HEK293 cells. Proteins for which binding to FAP could be confirmed were then used in combination with antibody fragments displayed on the surface of yeast in order to determine which sets of fragments bind distinct epitopes of FAP. Flow cytometry-based assays revealed that the isolated fragments recognize two or more distinct epitopes of the antigen. A handful of fragments is currently being subjected to affinity maturation and conversion to IgGs, and work to further investigate the in vitro and in vivo characteristics of the proteins is ongoing. These proteins may allow for the ablation of cancer-associated fibroblasts or interference with the proteolytic activity of FAP in the tumor microenvironment, providing biological insights into the roles of CAFs and therapeutic approaches to cancer treatment. Furthermore, the general antibody isolation and characterization approaches used in this work are accessible to many single-investigator laboratories and should be applicable to the targeting of numerous cancer antigens. Citation Format: James A. Van Deventer, Karl D. Wittrup. Targeting cancer-associated fibroblasts using antibodies recognizing fibroblast activation protein-alpha. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2138. doi:10.1158/1538-7445.AM2013-2138
Gastrointestinal Blood Pool Imaging in Tuberous Sclerosis
Authors: JAMES P. POLGA, SAID M. ZUBI, RICHARD P. SPENCER, ROBERT H. DANN
Journal: Clinical Nuclear Medicine (1985)

A Tc-99m RBC study of the abdomen, in a patient with tuberous sclerosis, showed an immediate “blush” due to a massive vascular malformation.