tbuckley/cabot-search huggingface dataset:
SCLERODERMA WITH PULMONARY FIBROSIS
Authors: John R. Murphy
Journal: JAMA (1941)

The pathologic changes in diffuse scleroderma are not confined to skin and subcutaneous tissue alone but involve the connective tissue system throughout the entire body. Muscle, fascia, tendon, bone and at times even the endocrine glands and the internal organs participate in the disease process. Everywhere the same changes occur, namely edema followed by sclerosis of the collagenous bundles. This may occur in the connective tissue between the alveoli of the lung, the acini of the liver, the glomeruli of the kidney and the muscle fibers of the heart and within the pulp of the spleen.<sup>1</sup>The smaller arteries within the regions involved show corresponding sclerotic degeneration and thickening of the intima which may proceed to obliteration of the lumen and subsequent focal necrosis.<sup>2</sup> The case to be presented is of interest because it has been possible to demonstrate visceral pathologic changes, namely pulmonary fibrosis or sclerosis as
Abstract 460: Delicate balance among three types of T cells in concurrent regulation of tumor immunity.
Authors: Liat Izhak, Elena Ambrosino, Jessica J. O'Konek, Shingo Kato, Stanley T. Parish, Zheng Xia, David Venzon, Jay A. Berzofsky, Masaki Terabe
Journal: Cancer Research (2013)

Abstract Various immunosuppressive cells, such as Tregs and type II NKT cells, mediate the immune regulation of cancer. Many studies have demonstrated the importance of regulatory cells; however, it is still not clear why different suppressive cells play a dominant role in different models. Here, we examined the relative role of two suppressors - Tregs and type II NKT cells – in a subcutaneous CT26 tumor model in three strains of mice: wild-type, NKT cell-deficient CD1dKO mice and Jα18KO, which lack type I NKT cells but still retain type II NKT cells. Tumors grew in all three strains, but Treg blockade by anti-CD25 mAb (PC61) led to tumor rejection in WT and CD1dKO but not in Jα18KO mice, suggesting that in Jα18KO mice, Tregs are not necessary for immune suppression. We hypothesized that cross regulation between type I and type II NKT cells in wild-type mice leaves Treg cells as primary suppressors, whereas in mice lacking type I NKT cells, unopposed type II NKT cells can suppress tumor immunity even when Tregs are blocked. We confirmed this hypothesis in PC61-treated Jα18KO mice by blocking type II NKT cells using anti-CD1d mAb (1B1) or by adoptive transfer of type I NKT cells combined with Treg blockade. These results support our hypothesis that it is necessary to block both suppressors, type II NKT cells and Tregs, in order to achieve protection. Also, activation of type II NKT cells by sulfatide in PC61-treated wild-type mice abrogated the protective effect of Treg blockade, indicating that shifting the balance between the two types of NKT cells toward immunosuppressive type II NKT cell dominance suppresses tumor immunity even in the absence of Tregs. We conclude that both Tregs and type II NKT cells can concurrently suppress tumor immunity and the balance between these is controlled in part by a third T cell, the type I NKT cell, regulating the regulators. Finally as cancer patients often have deficient type I NKT cell function somewhat like the Jα18KO mice, managing this delicate balance among three T cells may be critical for the success of immunotherapy of human cancer. Citation Format: Liat Izhak, Elena Ambrosino, Jessica J. O'Konek, Shingo Kato, Stanley T. Parish, Zheng Xia, David Venzon, Jay A. Berzofsky, Masaki Terabe. Delicate balance among three types of T cells in concurrent regulation of tumor immunity. [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 460. doi:10.1158/1538-7445.AM2013-460
Abstract 2793: Development of an androgen-dependent prostate Champions TumorGraft™ cancer model.
Authors: Tin Oo Khor, Keren Paz, Dhanrajan Tiruchinapalli, David Sidransky, Elizabeth M. Bruckheimer
Journal: Cancer Research (2013)

Abstract Prostate cancer (PCa)is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males, with the highest incidence rates recorded in developed countries such as those in North America (Jemal et al., 2011). While the five year-survival rate for PCa patients with localized disease is 100%, it is only 30.6% once the cancer metastasizes (Vishnu et al., 2010). One of the biggest challenges for finding a better treatment for metastatic PCa is the lack of predictable and accurate preclinical models that closely recapitulate different stages of the pathogenesis of human PCa. Champions Oncology focuses on the development of Champions TumorGraft™ models derived from the direct implantation of patient tumors into immunocompromised mice. Compared to traditional cell line-based xenograft models, the patient-derived TumorGraft models maintain stable gene-expression patterns and mutational status and correlate to clinical predictability. To overcome the challenge for PCa, Champions Oncology has utilized its TumorGraft technology to establish and characterize a new androgen-dependent prostate cancer TumorGraft model, CTG-0488. This involved the implantation of a primary human prostate tumor in immunocompromised mice in a manner that preserves the biological properties of the original human tumor. In this preliminary work, the characteristics of Champion TumorGraft™ model CTG-0488 are showcased, including tumor histology, mutational status, and chemosensitivity profiles to several standard of care compounds. Overall the development of an androgen-dependent prostate cancer Champions TumorGraft™ model will significantly aid in the development of oncology compounds focused on androgen-dependent prostate cancer. Citation Format: Tin Oo Khor, Keren Paz, Dhanrajan Tiruchinapalli, David Sidransky, Elizabeth M. Bruckheimer. Development of an androgen-dependent prostate Champions TumorGraft™ cancer model. [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 2793. doi:10.1158/1538-7445.AM2013-2793
Association of premature hair graying with family history, smoking, and obesity: A cross-sectional study
Authors: Hyoseung Shin, Hyeong Ho Ryu, Junghee Yoon, Seongmoon Jo, Sihyeok Jang, Mira Choi, Ohsang Kwon, Seong Jin Jo
Journal: Journal of the American Academy of Dermatology (2014)
681 Iron aggravates liver injury by triggering apoptosis in rat nutritional steatohepatitis
Authors: E. Eren, V. Tahan, N. Imeryuz, A. Sonsuz, C. Erzic, A. Ozer, G. Haklar, C. Celikel, E. Avsar, N. Tozun
Journal: Journal of Hepatology (2006)
Permanent Neurological Sequelae Despite Haemodialysis for Lithium Intoxication
Authors: B. von Hartitzsch, N. A. Hoenich, R. J. Leigh, R. Wilkinson, T. H. Frost, A. Weddel, G. A. Posen
Journal: BMJ (1972)

THREE PATIENTS WITH LITHIUM TOXICITY ARE REPORTED, TWO OF WHOM WERE EXPOSED TO TOXIC LITHIUM LEVELS FOR A PROLONGED PERIOD: both survived with permanent damage to basal ganglia and cerebellar connexions despite effective lowering of lithium levels by haemodialysis. Data obtained during dialysis treatment show prolonged haemodialysis to be the treatment of choice. If facilities for haemodialysis are not available or the patient presents with toxic lithium levels and minimal symptoms peritoneal dialysis will effectively lower serum lithium levels, but more slowly than haemodialysis.
One Hundred Primary Caudal Tumors
Authors: Craig W. Norstrom
Journal: JAMA (1961)

The authors have analyzed the diagnostic problems presented by 100 cases of primary tumors of the filum terminale internum and conus medullaris. The final diagnosis was made either at operation (99 cases) or at autopsy (1 case). The most frequent type was ependymoma (88 cases), and 80 of these involved the filum terminale internum. Of the total of 100 tumors, 52 involved the filum alone, 17 involved the conus alone, and 31 involved both structures. Initial diagnosis was difficult because the disturbances of both sensory and motor function so frequently resembled those of other conditions. Pain in the back was present in 91 cases, but it was vaguely localized, sometimes appeared to have been precipitated by trauma, and was not constant. The interval between onset of symptoms and surgical treatment was therefore about 3.2 years. In avoiding diagnostic errors, examination of the spinal fluid and lumbar myelography with air or a contrast medium are important.
Adenoviral Transduction of<i>MRP-1/CD9</i>and<i>KAI1/CD82</i>Inhibits Lymph Node Metastasis in Orthotopic Lung Cancer Model
Authors: Takayuki Takeda, Noboru Hattori, Takahiro Tokuhara, Yoshihiro Nishimura, Mitsuhiro Yokoyama, Masayuki Miyake
Journal: Cancer Research (2007)

Abstract Conventional therapies still remain less effective for metastasis of lung cancer, thus leading to a poor prognosis for this disorder. Although the processes involved in metastasis have not yet been clearly elucidated, our previous studies have shown that higher expression levels of MRP-1/CD9 and KAI1/CD82 in cancer cells are significantly correlated with less metastatic potency. To determine whether the gene transfer of these tetraspanins into lung tumor cells may be a useful strategy to regulate metastasis, we adopted an orthotopic lung cancer model produced by the intrapulmonary implantation of Lewis lung carcinoma (LLC) cells and evaluated the metastatic growth in the mediastinal lymph nodes using two different methods of gene delivery as follows: (a) the implantation of LLC cells preinfected with adenovirus encoding either MRP-1/CD9 cDNA, KAI1/CD82 cDNA, or LacZ gene into the mouse lung and (b) the intratracheal administration of these adenoviruses into the mice orthotopically preimplanted with LLC cells. In both cases, we found that the delivery of either MRP-1/CD9 or KAI1/CD82 cDNA dramatically reduced the metastases to the mediastinal lymph nodes in comparison with those of LacZ gene delivery, without affecting the primary tumor growth at the implanted site. These results reemphasize the important role of MRP-1/CD9 and KAI1/CD82 in the suppression of the metastatic process and also show the feasibility of gene therapy when using these tetraspanins for lung cancer to prevent metastasis to the regional lymph nodes. This strategy may therefore be clinically applicable as a prophylactic treatment to suppress the occurrence of lymph node metastasis. [Cancer Res 2007;67(4):1744–9]
NICE guideline focuses on diagnosis of acute chest pain to improve outcomes
Authors: Z. Kmietowicz
Journal: BMJ (2010)

Anyone who might be having a heart attack or has unstable angina should undergo 12 lead electrocardiography as soon as possible, say new guidelines from the UK National Institute for Health and Clinical Excellence (NICE). If patients need to be referred to hospital the result of the ECG should be sent ahead so it is there when they arrive, although recording and sending the result should not delay transfer to hospital, they say.

The guideline on chest pain of recent onset has been jointly developed with the National Clinical Guidelines Centre for Acute and Chronic Conditions. Unlike many guidelines from NICE, the latest advice does not cover treatment for chest pain but focuses only on diagnosis, with the aim of reducing premature deaths by differentiating between people with acute coronary syndrome and those with stable angina.

Chest pain accounts for up to 1% of visits …
PHARMACOPŒIAL NOMENCLATURE, AND THE LATIN OF PRESCRIPTIONS.Read before the Section of Materia Medica and Pharmacy, at the Forty-second Annual Meeting of the American Medical Association, Washington, D. C., May 1, 1891.
Authors: JOS. P. REMINGTON
Journal: JAMA (1891)

The frequent recurrence in current secular literature, and in halls of legislation, of the agitation against the use of Latin in prescribing and designating medicinal substances has developed a need for a strong expression of the well known advantages of the use of the Latin language in nomenclature. The pharmacist, because of his familiarity with the methods employed by many physicians, and on account of the large number of prescriptions which annually come under his critical observation, has by far the best opportunity for forming an accurate opinion of the relative value of the methods used in writing prescriptions, and the consensus of opinion is vastly in favor of retaining Latin. By far the larger number of prescriptions which are now compounded in the United States are written in Latin, but occasionally it will be found that a physician has formed the habit of writing in the vernacular. The general
Diminished beta-adrenergic receptor responsiveness and cardiac dilation in hearts of myopathic Syrian hamsters (BIO 53.58) are associated with a functional abnormality of the G stimulatory protein.
Authors: A M Feldman, R G Tena, P D Kessler, H F Weisman, S P Schulman, R S Blumenthal, D G Jackson, C Van Dop
Journal: Circulation (1990)

Previous studies have demonstrated a diminution in the bioactivity of the guanine nucleotide-binding regulatory protein that stimulates adenylyl cyclase (Gs) in hearts of the hypertrophic BIO 14.6 Syrian hamster. In this study, we measured functional activity and immunodetectable levels of Gs in a mutant strain of hamsters (BIO 53.58) that develop a dilated cardiomyopathy. Pathological studies demonstrated that 100-day-old BIO 53.58 hamsters had substantial ventricular dilation when compared with age-matched F1B controls. Additionally, these 100-day-old hamsters demonstrated diminished contractile response to beta-adrenergic receptor stimulation. The pathological and hemodynamic changes were associated with defective coupling of Gs to adenylyl cyclase as adenylyl cyclase activation was distinctly decreased in the presence of isoproterenol, fluoride ion, guanine nucleotides, and forskolin. Additionally, the ability of the alpha-subunit of Gs to reconstitute isoproterenol-stimulated adenylyl cyclase activity in S49 cyc- membranes was reduced approximately 65%. By contrast, cyc- complementation assays did not reveal a difference between the functional activity of Gs in hearts from 30-day-old BIO 53.58 hamsters and F1B controls. Furthermore, beta-adrenergic receptor stimulation of adenylyl cyclase in the membranes of the young BIO 53.58 hamsters was not significantly different from controls. The substantial alterations in Gs bioactivity in hearts of the 100-day-old BIO 53.58 hamsters was not associated with alterations in the immunodetectable levels of either alpha Gs or alpha Gi on Western Blots. These results suggest that G protein changes are associated with ventricular dilation in BIO 53.58 hamsters and that G protein levels are not always reflective of G protein bioactivity.
Poll highlights frustration with changes in UK medical training
Authors: Lynn Eaton
Journal: BMJ (2007)

A "cock-up" by the UK government has impeded the ability of the Healthcare Commission to assess independent sector treatment centres (ISTCs), says the watchdog's chief executive, Anna Walker.She says that a government oversight has impeded the commission's ability to assess the safety and quality of the centres.The commission declared this week that the Department of Health had failed to ensure that the data collected on the controversial clinics were compatible with the data used to monitor the rest of the NHS.The commission had aimed to review the first 23 centres, which were set up to carry out high volumes of straightforward elective surgery to cut NHS waiting lists.The commission interviewed 2000 patients, made inspections, and checked health records.Ms Walker said that there were gaps, however, because "comparative data has not been systematically collected."Where independent providers serve NHS patients we must ensure we have the proper systems to provide reassurance about what is being provided," she said."That is why we are calling for one sys-tem that allows comparable information to be published on all major healthcare providers, whether public or private, whether they are treating NHS patients or otherwise."Beginning in October, the Royal College of Surgeons will carry out its own study, funded by the Department of Health, to assess the success of operations carried out in the centres.Bernard Ribeiro, president of the Royal College of Surgeons, said, "It is imperative that patients receive a sustained, safe, and [high] quality service, which is consistent across surgical providers."See www.healthcarecommission.org.uk. Failure to monitor independent centres prevents comparison, say�s watchdog
HIV/AIDS demographics in US county and southeast England are similar
Authors: Stefan P Kruszewski
Journal: BMJ (2005)

Secondary prevention of heart disease with statins Groups were as different as chalk and cheeseEditor-Wei et al say that the results of their observational study of treatment with statins in routine clinical practice in Tayside are consistent with, and similar to, those reported in clinical trials. 1 This conclusion is hardly justified.A cohort of patients, defined by a discharge diagnosis of myocardial infarction between January 1993 and December 2001, was studied to compare the outcomes in those treated with statins and those not receiving these drugs.The data clearly show that the two groups differed substantially in terms of age, sex, comorbidity, and other cardiovascular drug treatment-all of these factors were biased in favour of a poorer outcome in patients not given statins.Furthermore, the two groups belonged to different time periods, most of the untreated patients to the earlier part and most of those given statins to the later part of the study.Given the changes between 1993 and 2001-including, for example, those related to the management of acute myocardial infarction and the criteria for diagnosis-it is only to be expected that the untreated group would have a higher risk of subsequent cardiovascular events.Multivariate analysis was reported as showing that statins reduced all cause mortality by 31% and the composite end point of myocardial infarction plus cardiovascular mortality by 18%.These results should be greeted with scepticism.Firstly, many trials of statins have failed to show any reduction whatsoever in all cause mortality. [2]][4][5] Secondly, as observed in other studies, any reduction in all cause mortality would be expected to be much less than that for composite cardiovascular end points. 2 4 5 The two groups in this study were as different as chalk and cheese.It should come as no surprise, therefore, that the results were anomalous.In such circumstances, no amount of statistical trickery could be expected to furnish anything of value.
Genetics of COPD: present and future
Authors: J.R. Hoidal
Journal: European Respiratory Journal (2001)

Chronic obstructive pulmonary disease (COPD) is a devastating clinical problem. In the USA, it affects >16 million people, accounts for 13% of hospitalizations, and is the fourth leading cause of death 1. Similarly, COPD is a major cause of morbidity and mortality worldwide. Over the next half-century, one and a half million deaths·yr−1 due to COPD are predicted in China alone 2. Although cigarette smoking is the major risk factor, only 10–20% of smokers develop symptomatic COPD. The extent of cigarette smoking (pack-yrs and duration of smoking) only account for ∼15% of the variation in lung function 3, indicating that differences in susceptibility to COPD must exist. Numerous epidemiological studies provide compelling evidence that genetic factors influence the development of COPD. Case-control studies have demonstrated an increased prevalence of COPD in relatives of patients with COPD that cannot be accounted for by known risk factors such as smoking 4–6. Twin studies also suggest a genetic basis to the development of COPD 7.

To date, α1-;antitrypsin (α1-;AT) deficiency remains the only proven genetic risk factor for COPD. The homozygous-deficient phenotype is rare (<0.1%), however, so only a small percentage (1–2%) of the genetic susceptibility to cigarette smoke is due to this phenotype. The best models of genetic components of COPD indicate that with the exception of α1-;AT it is a genetically complex disease 8. This is as expected given that the pathogenesis of COPD probably involves several cell types, enzymes and inflammatory mediators interacting in an intricate manner to influence the development of airways inflammation and parenchymal destruction.

For genetically complex diseases, recent emphasis has been placed on the common disease-common variant hypothesis, which states that common disease susceptibility or resistance variants are expected to be …
Antibody-dependent cellular cytotoxicity of the optimized anti-CD20 monoclonal antibody ublituximab on chronic lymphocytic leukemia cells with the 17p deletion
Authors: M Le Garff-Tavernier, L Herbi, C de Romeuf, F Nguyen-Khac, F Davi, A Grelier, M Boudjoghra, K Maloum, S Choquet, R Urbain, V Vieillard, H Merle-Béral
Journal: Leukemia (2013)
Polypeptide Hormones and Calcium Metabolism
Authors: G. D. AURBACH
Journal: Annals of Internal Medicine (1969)

Recent studies have expanded remarkably our understanding of the chemistry, physiology, mechanism of action, and clinical importance of the polypeptides—parathyroid hormone and thyrocalcitonin (calcitonin)—the principal hormones regulating calcium metabolism. Thyrocalcitonin, a hormone inducing hypocalcemia and hypophosphatemia, has been isolated, analyzed for amino acid sequence, and synthesized chemically. It is secreted from the parafollicular cells found in mammalian thyroid but related embryologically to the ultimobranchial body of lower vertebrate species. Sensitive radioimmunoassays for thyrocalcitonin and parathyroid hormone have shown that secretion of each is controlled by calcium. Current findings show that the major physiological actions of parathyroid hormone are mediated by adenosine 3′,5′-monophosphate (cyclic AMP) produced as a consequence of direct, specific hormonal stimulation of the enzyme adenyl cyclase in bone and kidney. Thyrocalcitonin acts through another mechanism to inhibit bone resorption. In normal subjects, but not in pseudohypoparathyroidism, parathyroid hormone causes a marked increase in urinary excretion of cyclic AMP. This observation forms the basis for a useful diagnostic test and suggests that the metabolic abnormality of pseudohypoparathyroidism may be attributable to a genetic lack or defect of a specific adenyl cyclase in renal and skeletal tissue.
Contrast-enhanced ultrasound-guided percutaneous cholangiography and cholangiodrainage (CEUS-PTCD)
Authors: A. Ignee, U. Baum, G. Schuessler, C. Dietrich
Journal: Endoscopy (2009)

We present our experience with contrast-enhanced ultrasound-guided percutaneous transhepatic cholangiodrainage in eight patients with obstructive jaundice and failure of conventional endoscopic retrograde cholangiography. The intraductal application of the ultrasound contrast agent led to sufficient cholangiography in all patients. In one patient, after accidental dislocation of the bile duct drain, the leakage could be detected by demonstration of the passage of contrast agent into the perihepatic peritoneal space. Further studies are necessary to evaluate this new technique in a larger numbers of patients.
Elimination of elder abuse would be fitting way to mark millennium
Authors: G. Bennett
Journal: BMJ (1998)

EDITOR—Badrinath and Ramaiah,1 in criticising the BMJ for failing to discuss elder abuse in an issue devoted to healthy ageing (25 October 1997), highlight something that should be a basic right for us all: to live a life free from the threat of violence. The importance of elder abuse to those who are abused and to the clinicians who care for them was indicated by the statement about elder …